ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.2354A>G (p.His785Arg)

dbSNP: rs1669452752
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001337331 SCV001530928 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2024-01-18 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 785 of the MSH6 protein (p.His785Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of MSH6-related conditions (PMID: 10612827). ClinVar contains an entry for this variant (Variation ID: 1034588). 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.
Baylor Genetics RCV003462906 SCV004195645 uncertain significance Endometrial carcinoma 2023-07-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV004651592 SCV005145621 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-10 criteria provided, single submitter clinical testing The p.H785R variant (also known as c.2354A>G), located in coding exon 4 of the MSH6 gene, results from an A to G substitution at nucleotide position 2354. The histidine at codon 785 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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