ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3200G>C (p.Ser1067Thr) (rs730881803)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160691 SCV000211313 uncertain significance not provided 2014-06-11 criteria provided, single submitter clinical testing This variant is denoted MSH6 c.3200G>C at the cDNA level, p.Ser1067Thr (S1067T) at the protein level, and results in the change of a Serine to a Threonine (AGT>ACT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH6 Ser1067Thr was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Serine and Threonine share similar properties, this is considered a conservative amino acid substitution. MSH6 Ser1067Thr occurs at a position that is well conserved across species and is not located in a known functional domain. In addition, in silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether MSH6 Ser1067Thr is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000205900 SCV000259950 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-10-08 criteria provided, single submitter clinical testing This sequence change replaces serine with threonine at codon 1067 of the MSH6 protein (p.Ser1067Thr). The serine residue is highly conserved and there is a small physicochemical difference between serine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MSH6-related disease. ClinVar contains an entry for this variant (Variation ID: 182644). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their 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.
Ambry Genetics RCV000563106 SCV000670024 uncertain significance Hereditary cancer-predisposing syndrome 2016-11-23 criteria provided, single submitter clinical testing Insufficient evidence
Counsyl RCV000663010 SCV000786022 uncertain significance Hereditary nonpolyposis colorectal cancer type 5 2018-02-09 criteria provided, single submitter clinical testing
Color RCV000563106 SCV000911938 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-17 criteria provided, single submitter clinical testing

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