ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.187G>A (p.Val63Met) (rs772216832)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Health, Inc RCV000664279 SCV001341287 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-13 criteria provided, single submitter clinical testing
Invitae RCV001342853 SCV001536801 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2020-08-11 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 63 of the PMS2 protein (p.Val63Met). The valine residue is weakly conserved and there is a small physicochemical difference between valine and methionine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in an individual with Lynch syndrome (PMID: 31845022). However, this individual also carried a pathogenic variant in MSH6. Therefore, the clinical significance of this variant (c.187G>A) is unclear. ClinVar contains an entry for this variant (Variation ID: 549723). 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 PMS2 protein function. 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.
True Health Diagnostics RCV000664279 SCV000788113 likely benign Hereditary cancer-predisposing syndrome 2017-11-16 no assertion criteria provided clinical testing

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