ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.680G>T (p.Ser227Ile) (rs587779317)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000075024 SCV000259596 uncertain significance Lynch syndrome 2015-07-25 criteria provided, single submitter clinical testing This sequence change replaces serine with isoleucine at codon 227 of the MSH6 protein (p.Ser227Ile). The serine residue is weakly conserved and there is a large physicochemical difference between serine and isoleucine. This variant is not present in the population databases (rs587779317, no frequency) and has been reported in the literature in a family affected with colorectal cancer (PMID: 16341805). However, whether or not this variant segregates with disease is unknown. While 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"), an algorithm specifically developed for the MSH6 suggests that this variant is likely to be neutral (PMID: 23621914). This prediction has not been confirmed by published functional studies. In summary, this is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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