Submissions for variant NM_000535.7(PMS2):c.137G>A (p.Ser46Asn) (rs121434629)

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Total submissions: 5

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000524431	SCV000552059	pathogenic	Hereditary nonpolyposis colon cancer	2019-10-21	criteria provided, single submitter	clinical testing	This sequence change replaces serine with asparagine at codon 46 of the PMS2 protein (p.Ser46Asn). The serine residue is highly conserved and there is a small physicochemical difference between serine and asparagine. This variant is present in population databases (rs121434629, ExAC 0.003%). This variant has been observed in individuals affected with clinical features of Lynch syndrome (PMID: 26866578, 25006859, Invitae). Also, this variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with constitutional mismatch repair deficiency syndrome (PMID: 18273873). ClinVar contains an entry for this variant (Variation ID: 91301). This variant has been reported to affect PMS2 protein function (PMID: 24027009). This variant disrupts the p.Ser46 amino acid residue in PMS2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22577899, 23709753). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Department of Pathology and Laboratory Medicine,Sinai Health System	RCV000076806	SCV000592922	likely pathogenic	Lynch syndrome	2014-12-11	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000584471	SCV000888391	likely pathogenic	not provided	2018-07-12	criteria provided, single submitter	clinical testing
Color	RCV001185073	SCV001351217	likely pathogenic	Hereditary cancer-predisposing syndrome	2019-10-24	criteria provided, single submitter	clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic	RCV000584471	SCV000691980	pathogenic	not provided		no assertion criteria provided	clinical testing

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