ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.2950A>C (p.Asn984His) (rs146359682)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166094 SCV000216860 uncertain significance Hereditary cancer-predisposing syndrome 2018-02-01 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000524150 SCV000260266 uncertain significance Hereditary nonpolyposis colon cancer 2019-11-11 criteria provided, single submitter clinical testing This sequence change replaces asparagine with histidine at codon 984 of the MSH6 protein (p.Asn984His). The asparagine residue is weakly conserved and there is a small physicochemical difference between asparagine and histidine. This variant is present in population databases (rs146359682, 0.07%). This variant has not been reported in the literature in individuals with MSH6-related disease. ClinVar contains an entry for this variant (Variation ID: 186492). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). However, an algorithm developed specifically for MSH6 (PMID: 23621914) suggests that this missense change is likely to be tolerated, although this prediction has not been confirmed by published functional studies. 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.
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000206584 SCV000296881 uncertain significance Lynch syndrome 2015-10-29 criteria provided, single submitter clinical testing
Color RCV000166094 SCV000685336 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-07 criteria provided, single submitter clinical testing
Counsyl RCV000662779 SCV000785588 uncertain significance Hereditary nonpolyposis colorectal cancer type 5 2017-09-25 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759855 SCV000889477 uncertain significance not provided 2017-09-18 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000662779 SCV001302729 uncertain significance Hereditary nonpolyposis colorectal cancer type 5 2017-04-27 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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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