Submissions for variant NM_000535.7(PMS2):c.955C>T (p.Pro319Ser)

dbSNP: rs1248142939

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000699703	SCV000828426	uncertain significance	Hereditary nonpolyposis colorectal neoplasms	2023-05-10	criteria provided, single submitter	clinical testing	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. 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 expected to disrupt PMS2 protein function. ClinVar contains an entry for this variant (Variation ID: 577045). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 319 of the PMS2 protein (p.Pro319Ser).
Color Diagnostics, LLC DBA Color Health	RCV000776634	SCV000912254	uncertain significance	Hereditary cancer-predisposing syndrome	2023-12-05	criteria provided, single submitter	clinical testing	This missense variant replaces proline with serine at codon 319 of the PMS2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PMS2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV000776634	SCV003887689	uncertain significance	Hereditary cancer-predisposing syndrome	2023-01-31	criteria provided, single submitter	clinical testing	The p.P319S variant (also known as c.955C>T), located in coding exon 9 of the PMS2 gene, results from a C to T substitution at nucleotide position 955. The proline at codon 319 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics	RCV003460964	SCV004207821	uncertain significance	Lynch syndrome 4	2023-06-04	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003999697	SCV004839873	uncertain significance	Lynch syndrome	2023-12-01	criteria provided, single submitter	clinical testing