ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.1050C>T (p.Ala350=) (rs730881802)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212643 SCV000211311 benign not specified 2014-08-21 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.
Ambry Genetics RCV000160690 SCV000215047 benign Hereditary cancer-predisposing syndrome 2014-11-18 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV001080910 SCV000283696 likely benign Hereditary nonpolyposis colorectal neoplasms 2020-12-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000409759 SCV000430957 uncertain significance Hereditary nonpolyposis colorectal cancer type 5 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Counsyl RCV000409759 SCV000489426 likely benign Hereditary nonpolyposis colorectal cancer type 5 2016-10-03 criteria provided, single submitter clinical testing
Color Health, Inc RCV000160690 SCV000537490 likely benign Hereditary cancer-predisposing syndrome 2015-08-04 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000212643 SCV000595840 likely benign not specified 2017-02-16 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212643 SCV000601500 uncertain significance not specified 2017-06-14 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000212643 SCV000695769 likely benign not specified 2019-08-29 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000586411 SCV000805836 likely benign not provided 2017-10-25 criteria provided, single submitter clinical testing
Mendelics RCV000409759 SCV001135801 likely benign Hereditary nonpolyposis colorectal cancer type 5 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000586411 SCV001250446 likely benign not provided 2020-01-01 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001356437 SCV001551604 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The MSH6 p.Ala350= variant was identified in 1 of 3786 proband chromosomes (frequency: 0.0003) from individuals or families with ovarian cancer (Pal 2012). The variant was also identified in dbSNP (ID: rs730881802) as "With other allele", ClinVar (classified as benign by GeneDx and Ambry Genetics; as likely benign by Invitae and four other submitters; as uncertain significance by three submitters). The variant was not identified in UMD-LSDB. The variant was identified in control databases in 18 of 276982 chromosomes at a frequency of 0.00007 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Other in 1 of 6468 chromosomes (freq: 0.0002), European in 16 of 126500 chromosomes (freq: 0.0001), Finnish in 1 of 25786 chromosomes (freq: 0.00004); it was not observed in the African, Latino, Ashkenazi Jewish, East Asian, and South Asian populations. The p.Ala350= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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