ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.916G>A (p.Val306Met) (rs587780063)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000656943 SCV000149619 uncertain significance not provided 2018-01-29 criteria provided, single submitter clinical testing This variant is denoted PMS2 c.916G>A at the cDNA level, p.Val306Met (V306M) at the protein level, and results in the change of a Valine to a Methionine (GTG>ATG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. PMS2 Val306Met was not observed at a significant frequency in large population cohorts (Lek 2016). This variant is located in the ATPase domain (Guarne 2001). 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 PMS2 Val306Met is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000115710 SCV000185566 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-29 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000469956 SCV000552057 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-12-15 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 306 of the PMS2 protein (p.Val306Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs587780063, ExAC 0.002%). This variant has been observed in an individual with colorectal cancer (PMID: 30521064). ClinVar contains an entry for this variant (Variation ID: 127801). 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: "Probably Damaging"; Align-GVGD: "Class C0"). 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 RCV000212856 SCV000601864 uncertain significance not specified 2016-08-31 criteria provided, single submitter clinical testing
Color RCV000115710 SCV000686257 uncertain significance Hereditary cancer-predisposing syndrome 2019-09-17 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000656943 SCV000806227 uncertain significance not provided 2018-01-10 criteria provided, single submitter clinical testing
Ding PR Lab,Sun Yat-sen University Cancer Center RCV001093686 SCV001250868 uncertain significance Lynch syndrome I no assertion criteria provided clinical testing

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