ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.984C>T (p.Ser328=) (rs138143769)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212638 SCV000170349 benign not specified 2014-02-14 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 RCV000126823 SCV000213111 likely benign Hereditary cancer-predisposing syndrome 2014-06-24 criteria provided, single submitter clinical testing This alteration is classified as likely 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 RCV001081374 SCV000252632 benign Hereditary nonpolyposis colorectal neoplasms 2020-11-25 criteria provided, single submitter clinical testing
Counsyl RCV000409252 SCV000488839 likely benign Hereditary nonpolyposis colorectal cancer type 5 2016-06-29 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000212638 SCV000595846 likely benign not specified 2017-04-17 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212638 SCV000601624 benign not specified 2017-05-01 criteria provided, single submitter clinical testing
Color Health, Inc RCV000126823 SCV000685532 benign Hereditary cancer-predisposing syndrome 2015-09-22 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000588033 SCV000695936 benign not provided 2016-01-04 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000212638 SCV000706960 likely benign not specified 2017-04-28 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000588033 SCV000889513 benign not provided 2017-05-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000212638 SCV001158617 benign not specified 2019-06-21 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000409252 SCV001302621 likely benign Hereditary nonpolyposis colorectal cancer type 5 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001355092 SCV001549867 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The MSH6 p.Ser328Ser= variant was not identified in the literature. The variant was identified in dbSNP (rs138143769) as “with uncertain significance, other allele”, ClinVar (classified as benign by Invitae, GeneDx, Color and 3 other submitters; and as likely benign by Ambry Genetics, Eurofins, Counsyl and 1 other submitter) and UMD-LSDB (observed 1x). The variant was identified in control databases in 81 of 282,780 chromosomes (1 homozygous) at a frequency of 0.0003 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 72 of 24,954 chromosomes (freq: 0.003, increasing the likelihood this could be a low frequency benign variant), Latino in 5 of 35,436 chromosomes (freq: 0.0001), and European in 4 of 129,118 chromosomes (freq: 0.00003), while it was not observed in the Ashkenazi Jewish, East Asian, Finnish, Other, or South Asian populations. The p.Ser328= 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. The variant occurs at a non-highly conserved nucleotide outside of the splicing consensus sequence and 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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