ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.713C>A (p.Ser238Tyr) (rs587782510)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131657 SCV000186684 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-20 criteria provided, single submitter clinical testing Insufficient evidence
GeneDx RCV000656889 SCV000279093 uncertain significance not provided 2018-09-20 criteria provided, single submitter clinical testing This variant is denoted MSH6 c.713C>A at the cDNA level, p.Ser238Tyr (S238Y) at the protein level, and results in the change of a Serine to a Tyrosine (TCT>TAT). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. MSH6 Ser238Tyr was not observed at a significant frequency in large population cohorts (Lek 2016). MSH6 Ser238Tyr is located within the nuclear localization signals (Gassman 2011). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether MSH6 Ser238Tyr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Counsyl RCV000410793 SCV000488368 uncertain significance Hereditary nonpolyposis colorectal cancer type 5 2016-03-08 criteria provided, single submitter clinical testing
Invitae RCV000472070 SCV000551284 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-12-13 criteria provided, single submitter clinical testing This sequence change replaces serine with tyrosine at codon 238 of the MSH6 protein (p.Ser238Tyr). The serine residue is weakly conserved and there is a large physicochemical difference between serine and tyrosine. This variant is present in population databases (rs587782510, ExAC 0.002%). This variant has not been reported in the literature in individuals with MSH6-related disease. ClinVar contains an entry for this variant (Variation ID: 142508). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000214572 SCV000601613 uncertain significance not specified 2016-11-23 criteria provided, single submitter clinical testing
Color RCV000131657 SCV000690474 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-09 criteria provided, single submitter clinical testing

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