ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.12G>C (p.Gln4His)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002380812 SCV002691099 uncertain significance Hereditary cancer-predisposing syndrome 2021-07-22 criteria provided, single submitter clinical testing The p.Q4H variant (also known as c.12G>C), located in coding exon 1 of the MSH6 gene, results from a G to C substitution at nucleotide position 12. The glutamine at codon 4 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV003465713 SCV004197566 uncertain significance Endometrial carcinoma 2023-10-29 criteria provided, single submitter clinical testing
Invitae RCV003594253 SCV004249226 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2024-01-18 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 4 of the MSH6 protein (p.Gln4His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 1769374). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MSH6 protein function with a negative predictive value of 95%. 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.
All of Us Research Program, National Institutes of Health RCV004007300 SCV004818641 uncertain significance Lynch syndrome 2023-03-28 criteria provided, single submitter clinical testing

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