Human Mutation
Volume 33, Issue 5 pp. 900-903
Errata
Free Access

A review of a multifactorial probability based model for classification of BRCA1 and BRCA2 variants of uncertain significance (VUS)

Noralane M. Lindor, 

Noralane M. Lindor

Departments of Medical Genetics, Mayo Clinic, Rochester, Minnesota

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Lucia Guidugli, 

Lucia Guidugli

Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota

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Xianshu Wang, 

Xianshu Wang

Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota

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Maxime P. Vallée, 

Maxime P. Vallée

International Agency for Research on Cancer, Lyon, France

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Alvaro N. A. Monteiro, 

Alvaro N. A. Monteiro

Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida

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Sean Tavtigian, 

Sean Tavtigian

Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah

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David E. Goldgar, 

David E. Goldgar

Department of Dermatology, University of Utah School of Medicine, Salt Lake City, Utah

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Fergus J. Couch, 

Fergus J. Couch

Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota

Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota

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First published: 13 April 2012
https://doi.org/10.1002/humu.22064
Citations: 3

The original article to which this Erratum refers was published in Human Mutation 33(1):8–21 (DOI 10.1002/humu.21627).

The authors realized that there was an error in Table 4 of their manuscript; a missense mutation in BRCA1 listed as R1495M should be considered Class 5, not Class 1, under that IARC class column on the far right Table 4 is published here in its corrected form. The genetic odds and prior probability shown for this alteration are listed correctly, but it was not mapped correctly to the IARC class.

The authors regret this error.

Table 4. BRCA1 VUS Classified as Class 1, 2 or Class 4, 5
BRCA1 exon Codon HGVS: protein level BIC: DNA level HGVS: DNA level Odds in favor of causality Reference Prior probability of being deleterious Posterior probability of being deleterious IARC class
2 M18T p.Met18Thr 172T>C c.53T>C 31.61 Easton et al., 2007 0.66 0.98 4
2 L22S p.Leu22Ser 184T>C c.65T>C 38.88 Sweet et al., 2010 0.81 0.99 5
3 T37K p.Thr37K 229C>A c.110C>A 634.47 Sweet et al., 2010 0.81 1.00 5
3 C39R p.Cys39Arg 234T>C c.115T>C 34.60 Sweet et al., 2010 0.81 0.99 5
3 C44S p.Cys44Ser 249T>A c.130T>A 149.60 Sweet et al., 2010 0.81 1.00 5
3 C44Y p.Cys44Tyr 250G>A c.131G>A 83.48 Sweet et al., 2010 0.81 1.00 5
3 K45Q p.Lys45Gln 252A>C c.133A>C 0.03 Sweet et al., 2010 0.03 8.00 × 10 1
5 C61G p.Cys61Gly 300T>G c.181T>G 1285.43 Spearman et al., 2008 0.81 1.00 5
5 D67Y p.Asp67Tyr 318G>T c.199G>T 9.38 × 10−5 Easton et al., 2007 0.03 2.90 × 10−6 1
7 Y105C p.Tyr105Cys 433A>G c.314A>G 5.15 × 10−6 Easton et al., 2007 0.02 1.05 × 10−7 1
7 I124V p.Ile124Val 489A>G c.370A>G 6.80 × 10−3 Easton et al., 2007 0.02 1.39 × 10−4 1
7 N132K p.Asn132Lys 515C>A c.396C>A 8.13 × 10−3 Easton et al., 2007 0.02 1.66 × 10−4 1
7 P142H p.Pro142His 544C>A c.425C>A 5.04 × 10−5 Chenevix-Trench et al., 2006 0.02 1.03 × 10−6 1
7 E143K p.Glu143Lys 546G>A c.427G>A 5.35 × 10−4 Easton et al., 2007 0.02 1.09 × 10−5 1
8 Q155E p.Gln155Glu 582C>G c.463C>G 1.91 × 10−3 Easton et al., 2007 0.02 3.89 × 10−5 1
8 Y179C p.Tyr179Cys 655A>G c.536A>G 8.50 × 10−11 Spurdle et al., 2008 0.02 1.73 × 10−12 1
9 S186Y p.Ser186Tyr 676C>A c.557C>A 3.83 × 10−10 Easton et al., 2007 0.02 7.82 × 10−12 1
9 V191I p.Val191Ile 690G>A c.571G>A 7.69 × 10−6 Easton et al., 2007 0.02 1.57 × 10−7 1
11 L246V p.Leu246Val 855T>G c.736T>G 2.60 × 10−5 Tavtigian et al., 2006 0.02 5.31 × 10−7 1
11 A280G p.Ala280Gly 958C>G c.839C>G 3.76 × 10−3 Easton et al., 2007 0.02 7.67 × 10−5 1
11 M297I p.Met297Ile 1010G>A c.891G>A 3.11 × 10−3 Easton et al., 2007 0.02 6.34 × 10−5 1
11 P334H p.Pro334His 1120C>A c.1001C>A 1.34 Spearman et al., 2008 0.02 0.02 2
11 P334L p.Pro334Leu 1120C>T c.1001C>T 1.33 × 10−5 Easton et al., 2007 0.02 2.71 × 10−7 1
11 Q356R p.Gln34Arg 1186A>G c.1067A>G <1.00 × 10−10 Tavtigian et al., 2006 0.02 <2.04 × 10−12 1
11 D369del p.Asp369del 1225del3 c.1105_1107del 3.00 × 10−4 Easton et al., 2008 0.02 6.13 × 10−6 1
11 D369N p.Asp369Asn 1224G>A c.1105G>A 2.78 × 10−4 Easton et al., 2007 0.02 5.68 × 10−6 1
11 D420Y p.Asp420Tyr 1377G>T c.1258G>T 0.01 Easton et al., 2007 0.02 1.66 × 10−4 1
11 N473S p.Asn473Ser 1537A>G c.1418A>G 1.65 × 10−4 Easton et al., 2007 0.02 3.37 × 10−6 1
11 F486L p.Phe486Leu 1575T>C c.1456T>C 9.13 × 10−11 Spurdle et al., 2008 0.02 1.86 × 10−12 1
11 R496H p.Arg496His 1606G>A c.1487G>A 9.20 × 10−5 Tavtigian et al., 2006 0.02 1.88 × 10−6 1
11 R496C p.Arg496Cys 1605C>T c.1486C>T 0.04 Chenevix-Trench et al., 2006 0.02 8.91 × 10−4 1
11 R504H p.Arg504His 1630G>A c.1511G>A 5.21 × 10−5 Easton et al., 2007 0.02 1.06×10−6 1
11 N550H p.Asn550His 1767A>C c.1648A>C 8.00 × 10−11 Spurdle et al., 2008 0.02 1.63 × 10−12 1
11 E597K p.Glu597Lys 1908G>A c.1789G>A 3.40 × 10−9 Easton et al., 2007 0.02 6.92 ×10−11 1
11 A622V p.Ala622Val 1984C>T c.1865C>T 1.00 × 10−3 Easton et al., 2007 0.02 2.12× 10−5 1
11 D642H p.Asp642His 2043G>C c.1924G>C 6.87 × 10−4 Easton et al., 2007 0.02 1.40 × 10−5 1
11 K654Q p.Lys654Gln 2079A>C c.1960A>C 0.34 Osorio et al., 2007 0.02 6.86 × 10−3 2
11 L668F p.Leu668Phe 2121C>T c.2002C>T 9.52 × 10−3 Easton et al., 2007 0.02 1.94 × 10−4 1
11 D693N p.Asp693Asn 2196G>A c.2077G>A 1.00 × 10−10 Tavtigian et al., 2006 0.02 2.04 × 10−12 1
11 N723D p.Asn723Asp 2286A>G c.2167A>G 1.55 × 10−8 Easton et al., 2007 0.02 3.17 × 10−10 1
11 E736A p.Glu736Ala 2326A>C c.2207A>C 0.48 Spearman et al., 2008 0.02 9.62 × 10−3 2
11 V772A p.Val772Ala 2434T>C c.2315T>C 9.40 × 10−6 Tavtigian et al., 2006 0.02 1.92 × 10−7 1
11 Q804H p.Gln804His 2531G>C c.2412G>C 0.02 Chenevix-Trench et al., 2006 0.02 4.46 × 10−4 1
11 N810Y p.Asn810Tyr 2547A>T c.2428A>T 1.14 × 10−11 Easton et al., 2007 0.02 2.33 × 10−13 1
11 K820E p.Lys820Gln 2577A>G c.2458A>G <1.00 × 10−10 Tavtigian et al., 2006 0.02 <2.04 × 10−12 1
11 T826K p.Thr826Lys 2596C>A c.2477C>A 9.97 × 10−8 Spurdle et al., 2008 0.02 2.03 × 10−9 1
11 R841W p.Arg841Trp 2640C>T c.2521C>T 1.12 × 10−10 Goldgar et al., 2004 0.02 2.29 × 10−12 1
11 E842G p.Glu842Gly 2644A>G c.2525A>G 2.11 × 10−4 Easton et al., 2007 0.02 4.30 ×10−6 1
11 Y856H p.Tyr856His 2685T>C c.2566T>C 8.80 × 10−3 Tavtigian et al., 2006 0.02 1.80 × 10−4 1
11 K862E p.Lys862Glu 2703A>G c.2584A>G 4.86 × 10−4 Easton et al., 2007 0.02 9.91 × 10−6 1
11 R866C p.Arg866Cys 2715C>T c.2596C>T 8.00 × 10−13 Easton et al., 2007 0.02 1.63 × 10−14 1
11 P871L p.Pro871Leu 2731C>T c.2612C>T <1.00 × 10−10 Tavtigian et al., 2006 0.02 <2.04 × 10−12 1
11 G890V p.Gly890Val 2788G>T c.2669G>T 2.00 × 10−4 Easton et al., 2007 0.02 4.08 × 10−6 1
11 V920A p.Val920Ala 2878T>C c.2759T>C 1.02 Spurdle et al., 2008 0.02 0.02 2
11 I925L p.Ile925Leu 2892A>C c.2773A>C 1.6 × 10−4 Easton et al., 2007 0.02 3.26 × 10−6 1
11 M1008I p.Met1008Ile 3143G>A c.3024G>A 9.6 × 10−7 Tavtigian et al., 2006 0.02 1.96 × 10−8 1
11 M1008V p.Met1008Val 3141A>G c.3022A>G <1.00 × 10−10 Tavtigian et al., 2006 0.02 <2.04 × 10−12 1
11 R1028H p.Arg1028His 3202G>A c.3083G>A 4.90 × 10−4 Easton et al., 2007 0.02 9.98 × 10−6 1
11 E1038G p.Gln1038Gly 3232A>G c.3113A>G <1.00 × 10−10 Tavtigian et al., 2006 0.02 <2.04 × 10−12 1
11 S1040N p.Ser1040Asn 3238G>A c.3119G>A <1.00 × 10−10 Tavtigian et al., 2006 0.02 <2.04 × 10−12 1
11 I1044V p.Ile1044Val 3249A>G c.3130A>G 1.15×10−4 Easton et al., 2007 0.02 2.34 × 10−6 1
11 P1099L p.Pro1099Leu 3415C>T c.3296C>T 1.52 × 10−9 Spurdle et al., 2008 0.02 3.09 × 10−11 1
11 S1101N p.Ser1101Asn 3421G>A c.3302G>A 3.10 × 10−7 Easton et al., 2007 0.02 6.32 × 10−9 1
11 K1109N p.Lys1109Asn 3446A>C c.3327A>C 1.51 × 10−3 Easton et al., 2007 0.02 3.07 × 10−5 1
11 S1140G p.Ser1140Gly 3537A>G c.3418A>G 2.90 × 10−4 Tavtigian et al., 2006 0.02 5.92 × 10−6 1
11 D1155H p.Asp1155His 3582G>C c.3463G>C 3.50 × 10−4 Chenevix-Trench et al., 2006 0.02 7.14 × 10−6 1
11 K1183R p.Lys1183Arg 3667A>G c.3548A>G <1.00 × 10−10 Tavtigian et al., 2006 0.02 <2.04 × 10−12 1
11 Q1200H p.Gln1200His 3719G>C c.3600G>C 0.35 Osorio et al., 2007 0.02 7.09 × 10−3 2
11 R1203Q p.Arg1203Gln 3727G>A c.3608G>A 1.79 × 10−4 Easton et al., 2007 0.02 3.65 × 10−6 1
11 E1214K p.Glu1214Lys 3759G>A c.3640G>A 3.38 × 10−8 Easton et al., 2007 0.02 6.89 × 10−10 1
11 P1238L p.Pro1238Leu 3832C>T c.3713C>T 9.52 × 10−7 Easton et al., 2007 0.02 1.94 × 10−8 1
11 V1247I p.Val1247Ile 3858G>A c.3739G>A 1.23 × 10−4 Easton et al., 2007 0.02 2.51 × 10−6 1
11 E1250K p.Glu1250Lys 3867G>A c.3748G>A 1.00×10−5 Tavtigian et al., 2006 0.02 2.04 × 10−7 1
11 S1266T p.Ser1266Thr 3916G>C c.3797G>C 5.56 × 10−5 Easton et al., 2007 0.02 1.13 × 10−6 1
11 I1275V p.Ile1275Val 3942A>G c.3823A>G 1.62 × 10−5 Easton et al., 2007 0.02 3.31 × 10−7 1
11 R1347G p.Arg1347Gly 4158A>G c.4039A>G <1.00 × 10−10 Tavtigian et al., 2006 0.02 <2.04 × 10−12 1
11 T1349M p.Thr1349Met 4165C>T c.4046C>T 2.16 × 10−3 Easton et al., 2007 0.02 4.42×10−5 1
11 M1361L p.Met1361Leu 4200A>C c.4081A>C 9.62 × 10−3 Easton et al., 2007 0.02 1.96 × 10−4 1
13 H1402Y p.His1402Tyr 4323C>T c.4204C>T 6.06 × 10−3 Easton et al., 2007 0.03 1.87 × 10−4 1
13 E1419Q p.Glu1419Gln 4374G>C c.4255G>C 4.93 × 10−3 Easton et al., 2007 0.03 1.52 × 10−4 1
13 R1443G p.Arg1443Gly 4446C>G c.4327C>G <0.02 Carvalho et al., 2007 0.03 <6.18 × 10−4 1
14 N1468H p.Asn1468His 4521A>C c.4402A>C 2.97 × 10−3 Easton et al., 2007 0.03 9.18 × 10−5 1
14 aR1495M p.Arg1495Met 4603G>T c.4484G>T 1.25 × 106 Easton et al., 2007 0.81 1.00 5
15 S1512I p.Ser1512Ile 4654G>T c.4535G>T <1.00 × 10−10 Tavtigian et al., 2006 0.03 <3.09 × 10−12 1
15 V1534M p.Val1534Met 4719G>A c.4600G>A 2.39 × 10−9 Easton et al., 2007 0.03 7.40 × 10−11 1
15 D1546N p.Asp1546Asn 4755G>A c.4636G>A 5.60 × 10−3 Tavtigian et al., 2006 0.03 1.73×10−4 1
15 D1546Y p.Asp1546Tyr 4755G>T c.4636G>T 9.19 × 10−4 Easton et al., 2007 0.03 2.84 × 10−5 1
16 L1564P p.Leu1564Pro 4810T>C c.4691T>C 3.30 × 10−3 Tavtigian et al., 2006 0.03 1.02 × 10−4 1
16 S1613G p.Ser1613Gly 4956A>G c.4837A>G <1.00×10−10 Tavtigian et al., 2006 0.03 <3.09 × 10−12 1
16 P1614S p.Pro1614Ser 4959C>T c.4840C>T 2.27 × 10−9 Easton et al., 2007 0.03 7.03 × 10−11 1
16 M1628T p.Met1628Thr 5002T>C c.4883T>C 1.60 × 10−4 Tavtigian et al., 2006 0.03 4.95 × 10−6 1
16 P1637L p.Pro1637Leu 5029C>T c.4910C>T 2.03 × 10−3 Easton et al., 2007 0.03 6.27 × 10−5 1
16 M1652I p.Met1652Ile 5075G>A c.4956G>A 4.80×10−4 Osorio A et al., 2007 0.03 1.48 × 10−5 1
16 M1652T p.Met1652Thr 5074T>C c.4955T>C 2.68 × 10−4 Easton et al., 2007 0.29 1.10 × 10−4 1
16 F1662S p.Phe1662Ser 5104T>C c.4985T>C 5.21 × 10−3 Easton et al., 2007 0.03 1.61 × 10−4 1
17 E1682K p.Glu1682Lys 5163G>A c.5044G>A 3.15 × 10−3 Easton et al., 2007 0.03 9.76 × 10−5 1
17 T1685A p.Thr1685Ala 5172A>G c.5053A>G 107.00 Easton et al., 2007 0.66 1.00 5
17 T1685I p.Thr1685Ile 5173C>T c.5054C>T 140.00 Easton et al., 2007 0.81 1.00 5
17 V1688del p.Val1688del 5181del3 c.5181_5183delGTT 268.00 Easton et al., 2007 0.81 1.00 5
17 M1689R p.Met1689Arg 5185T>G c.5066T>G 46.00 Easton et al., 2007 0.66 0.989 4
18 R1699Q p.Arg1699Gln 5215G>A c.5096G>A 142.00 Chenevix-Trench et al., 2006 0.66 1.00 5
18 R1699W p.Arg1699Trp 5214C>T c.5095C>T 4.00 × 104 Easton et al., 2007 0.81 1.00 5
18 G1706A p.Gly1706Ala 5236G>C c.5117G>C 2.55 × 10−5 Lovelock et al., 2006 0.66 4.95 × 10−5 1
18 G1706E p.Gly1706Glu 5236G>A c.5117G>A 589.00 Easton et al., 2007 0.81 1.00 5
18 A1708E p.Ala1708Glu 5242C>A c.5123C>A 2.11×1012 Easton et al., 2007 0.81 1.00 5
18 S1715R p.Ser1715Arg 5262A>C c.5143A>C 45.00 Easton et al., 2007 0.81 0.99 5
19 T1720A p.Thr1720Ala 5277A>G c.5158A>G 1.11 × 10−11 Easton et al., 2007 0.03 3.44 × 10−13 1
20 G1738R p.Gly1738Arg 5331G>A c.5212G>A 114.00 Easton et al., 2007 0.81 1.00 5
20 R1751Q p.Arg1751Gln 5371G>A c.5252G>A 6.67 × 10−3 Easton et al., 2007 0.03 2.06 × 10−4 1
21 L1764P p.Leu1764Pro 5410T>C c.5291T>C 350.00 Easton et al., 2007 0.29 0.99 5
21 I1766S p.Ile1766Ser 5416T>G c.5297T>G 139.00 Easton et al., 2007 0.66 1.00 5
21 M1775K p.Met1775 Lys 5443T>A c.5324T>A 235.00 Tischkowitz et al., 2008 0.66 1.00 5
21 M1775R p.Met1775Arg 5443T>G c.5324T>G >1000 Carvalho et al., 2007 0.66 1.00 5
21 P1776H p.Pro1776His 5446C>A c.5327C>A 1.04 Spearman et al., 2008 0.03 0.03 2
22 C1787S p.Cys1787Ser 5478T>A c.5359T>A 2032.80 Goldgar et al., 2004 0.81 1.00 5
22 G1788V p.Gly1788Val 5482G>T c.5363G>T 7054.00 Easton et al., 2007 0.81 1.00 5
23 V1804D p.Val1804Asp 5530T>A c.5411T>A 1.21 × 10−3 Easton et al.,2007 0.03 3.74 × 10−5 1
24 V1838E p.Val1838Glu 5632T>A c.5513T>A 3973.97 Spurdle et al., 2008 0.66 1.00 5
24 I1858L p.Ile1858Leu 5691A>C c.5572A>C 2.25×10−3 Easton et al., 2007 0.03 6.97 × 10−5 1
24 P1859R p.Pro1859Arg 5695C>G c.5576C>G 3.35 × 10−5 Easton et al., 2007 0.03 1.04 × 10−6 1
  • aVUS shown to result in aberrant gene splicing
  • GenBank Reference BRCA1 U14680.1
  • Nucleotide numbering in “HGVS: DNA level” reflects cDNA numbering with +1 corresponding to the A of the ATG translation initiation codon in the reference sequence, according to journal guidelines (www.hgvs.org/mutnomen). The initiation codon is codon 1.
  • Nucleotide numbering in “BIC-DNA level” refers to the original nomenclature for BRCA1 and BRCA2 before adoption of HGVS standards where BRCA1 +119 and BRCA2 +228 correspond to the A of the ATG translation initiation codons in the reference sequence.

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