ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3478G>T (p.Val1160Phe) (rs376799914)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164110 SCV000214724 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000466573 SCV000551043 uncertain significance Hereditary nonpolyposis colon cancer 2018-07-15 criteria provided, single submitter clinical testing This sequence change replaces valine with phenylalanine at codon 1160 of the MSH6 protein (p.Val1160Phe). The valine residue is highly conserved and there is a small physicochemical difference between valine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MSH6-related disease. ClinVar contains an entry for this variant (Variation ID: 184794). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000506000 SCV000604279 uncertain significance not specified 2017-01-06 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000589252 SCV000695868 uncertain significance not provided 2016-06-20 criteria provided, single submitter clinical testing Variant summary: The MSH6 c.3478G>T (p.Val1160Phe) variant causes a missense change involving the alteration of a conserved nucleotide with 4/4 in silico tools (SNPs&GO not captured here due to low reliability index) predicting a damaging outcome, although these predictions have yet to be functionally assessed. The variant of interest was not observed in controls (ExAC, 1000 Gs or ESP), nor has it been, to our knowledge, reported in affected individuals via publications. A clinical laboratory has cited the variant as "uncertain significance." Therefore, due to the limited clinical and functional data, the variant of interest is classified as a "Variant of Uncertain Significance," until additional information becomes available.
Counsyl RCV000663282 SCV000786521 uncertain significance Hereditary nonpolyposis colorectal cancer type 5 2018-05-18 criteria provided, single submitter clinical testing

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