ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.957G>A (p.Thr319=) (rs375210430)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000215946 SCV000276424 likely benign Hereditary cancer-predisposing syndrome 2015-06-10 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.
GeneDx RCV000421305 SCV000516555 benign not specified 2015-05-27 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.
Invitae RCV001087378 SCV000561443 likely benign Hereditary nonpolyposis colorectal neoplasms 2020-11-10 criteria provided, single submitter clinical testing
Color Health, Inc RCV000215946 SCV000685530 likely benign Hereditary cancer-predisposing syndrome 2017-02-17 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000475129 SCV001152289 likely benign not provided 2017-06-01 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001355644 SCV001550587 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The MSH6 p.Thr319= variant was not identified in the literature nor was it identified in the Genesight-COGR, UMD-LSDB, Insight Colon Cancer Gene Variant Database, Zhejiang Colon Cancer Database, Mismatch Repair Genes Variant Database, Insight Hereditary Tumors Database, databases. The variant was identified in dbSNP (ID: rs375210430) as With Likely benign allele, ClinVar (classified as benign by GeneDx; classified as likely benign by Ambry Genetics, Invitae), Clinvitae (classified as likely benign by ClinVar), Cosmic (neutral (score 0.17) ), databases. The variant was identified in control databases in 7 of 246054 chromosomes at a frequency of 0.00003 in the following populations: SouthAsian in 3 of 30780 chromosomes (freq. 0.0001), European in 2 of 111556 chromosomes (freq.0.00002), Latino in 1 of 33574 chromosomes (freq. 0.00003), EastAsian in 1 of 17246 chromosomes (freq. 0.0001) increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017). The p.Thr319= 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, HumanSpliceFinder) 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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