ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.2633T>C (p.Val878Ala) (rs2020912)

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Total submissions: 21
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000121581 SCV000604268 likely benign not specified 2016-08-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV000157763 SCV000212713 benign Hereditary cancer-predisposing syndrome 2014-11-18 criteria provided, single submitter clinical testing
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034495 SCV000043358 no known pathogenicity not provided 2012-07-13 no assertion criteria provided research Converted during submission to Benign.
CSER_CC_NCGL; University of Washington Medical Center RCV000148644 SCV000190359 likely benign Colorectal / endometrial cancer 2014-06-01 no assertion criteria provided research
Color RCV000157763 SCV000537378 benign Hereditary cancer-predisposing syndrome 2015-01-02 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000009486 SCV000744292 benign Hereditary nonpolyposis colorectal cancer type 5 2015-09-21 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000121581 SCV000592611 likely benign not specified 2013-04-15 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000009486 SCV000734215 benign Hereditary nonpolyposis colorectal cancer type 5 no assertion criteria provided clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000121581 SCV000854909 likely benign not specified 2018-02-23 criteria provided, single submitter clinical testing
GeneDx RCV000121581 SCV000170356 benign not specified 2013-10-11 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Genetic Services Laboratory, University of Chicago RCV000121581 SCV000595842 likely benign not specified 2016-08-16 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000009486 SCV000743210 benign Hereditary nonpolyposis colorectal cancer type 5 2017-07-28 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory,VU University Medical Center Amsterdam RCV000009486 SCV000745652 likely benign Hereditary nonpolyposis colorectal cancer type 5 2015-09-22 criteria provided, single submitter clinical testing
ITMI RCV000121581 SCV000085777 not provided not specified 2013-09-19 no assertion provided reference population
Integrated Genetics/Laboratory Corporation of America RCV000121581 SCV000695820 benign not specified 2016-04-25 criteria provided, single submitter clinical testing Variant summary: Variant affects a non-conserved nucleotide and results in a replacement of a medium size and hydrophobic Valine (V) with a small size and hydrophobic Alanine (A). 2/3 in silico tools predict the variant to be neutral (SNPs&GO and mutation taster were not considered due to low reliability index). The variant was observed in the large and broad cohorts of the ExAC project across diverse ethnicities at an allele frequency of 0.52% which exceeds ~ 36 times the maximal expected allele frequency of a disease causing MSH6 allele (0.0142%). Additionally, 4 homozygous occurrences are also reported in ExAC indicating neutrality. The variant was reported in several patients, however without strong evidence for pathogenicity. Independent functional studies concluded the variant to slightly impair MSH6 MMR functions however a large case control study failed to show association between CRC and the variant (Lipkin_NG_2004). Several clinical diagnostic centers and databases classify variant as Benign (without evidence to independently evaluate). Moreover, UMD lists two co-occurrences with the following pathogenic MSH6 variants: c.3268_3274del (p.Glu1090LysfsX23) and c.3514dup (p.Arg1172LysfsX5). Considering all evidence, the variant was classified as Benign.
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000030264 SCV000107978 no known pathogenicity Lynch syndrome 2013-09-05 reviewed by expert panel research Multifactorial likelihood analysis posterior probability <0.001
Invitae RCV000524148 SCV000153945 benign Hereditary nonpolyposis colon cancer 2018-01-25 criteria provided, single submitter clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000121581 SCV000257226 benign not specified no assertion criteria provided clinical testing
OMIM RCV000009486 SCV000029704 uncertain significance Hereditary nonpolyposis colorectal cancer type 5 2001-10-01 no assertion criteria provided literature only
PreventionGenetics RCV000121581 SCV000302872 benign not specified criteria provided, single submitter clinical testing
True Health Diagnostics RCV000157763 SCV000788047 benign Hereditary cancer-predisposing syndrome 2018-09-11 no assertion criteria provided clinical testing

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