ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.957G>C (p.Thr319=)

gnomAD frequency: 0.00002  dbSNP: rs375210430
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000232871 SCV000283861 likely benign Hereditary nonpolyposis colorectal neoplasms 2024-01-25 criteria provided, single submitter clinical testing
Ambry Genetics RCV000571890 SCV000662355 likely benign Hereditary cancer-predisposing syndrome 2015-03-20 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Color Diagnostics, LLC DBA Color Health RCV000571890 SCV000690492 likely benign Hereditary cancer-predisposing syndrome 2017-07-26 criteria provided, single submitter clinical testing
GeneDx RCV000610225 SCV000729024 benign not specified 2015-05-26 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.
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001354904 SCV001549628 likely benign Lynch syndrome no assertion criteria provided clinical testing The MSH6 p.Thr319= variant was not identified in the literature nor was it identified in the COGR, Cosmic, UMD-LSDB, Zhejiang University Database, Mismatch Repair Genes Variant Database, or Insight Hereditary Tumors Database. The variant was identified in dbSNP (ID: rs375210430) as "With Likely benign allele", and in ClinVar (classified as likely benign by Invitae, Ambry Genetcs, Color Genomics, GeneDx). The variant was identified in control databases in 4 of 246054 chromosomes at a frequency of 0.00002 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Latino in 1 of 33574 chromosomes (freq: 0.00003), European in 3 of 111556 chromosomes (freq: 0.00003), it was not observed in the African, Other, Ashkenazi Jewish, East Asian, Finnish, and South Asian populations. 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) 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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