ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.1078A>G (p.Ser360Gly) (rs145994565)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000479215 SCV000568178 uncertain significance not specified 2017-04-26 criteria provided, single submitter clinical testing This variant is denoted MSH6 c.1078A>G at the cDNA level, p.Ser360Gly (S360G) at the protein level, and results in the change of a Serine to a Glycine (AGT>GGT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH6 Ser360Gly was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. Since Serine and Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. MSH6 Ser360Gly occurs at a position that is not conserved and is located within the MSH2 binding site (Kariola 2002). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether MSH6 Ser360Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000479215 SCV000601502 uncertain significance not specified 2017-01-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV000563224 SCV000662405 uncertain significance Hereditary cancer-predisposing syndrome 2017-11-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000629709 SCV000750665 uncertain significance Hereditary nonpolyposis colon cancer 2018-12-31 criteria provided, single submitter clinical testing This sequence change replaces serine with glycine at codon 360 of the MSH6 protein (p.Ser360Gly). The serine residue is weakly conserved and there is a small physicochemical difference between serine and glycine. This variant is present in population databases (rs145994565, ExAC 0.009%). This variant has not been reported in the literature in individuals with MSH6-related disease. ClinVar contains an entry for this variant (Variation ID: 419950). An algorithm developed specifically for the MSH6 gene suggests that this missense change is likely to be tolerated (PMID: 23621914). However, this prediction has not been confirmed by published functional studies and its 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.
Color RCV000563224 SCV000911254 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-16 criteria provided, single submitter clinical testing

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