Submissions for variant NM_000535.7(PMS2):c.1041G>C (p.Glu347Asp)

dbSNP: rs150515238

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000115648	SCV000149557	uncertain significance	not provided	2024-12-27	criteria provided, single submitter	clinical testing	Observed in an individual with a personal and family history of Lynch syndrome-related cancers (PMID: 31350202); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 32210335, 30787465, 11574484, 31350202)
Counsyl	RCV000411537	SCV000487856	uncertain significance	Lynch syndrome 4	2015-11-23	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000458229	SCV000552038	likely benign	Hereditary nonpolyposis colorectal neoplasms	2024-11-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000565848	SCV000670863	uncertain significance	Hereditary cancer-predisposing syndrome	2024-08-05	criteria provided, single submitter	clinical testing	The p.E347D variant (also known as c.1041G>C), located in coding exon 10 of the PMS2 gene, results from a G to C substitution at nucleotide position 1041. The glutamic acid at codon 347 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health	RCV000565848	SCV001353141	uncertain significance	Hereditary cancer-predisposing syndrome	2022-01-21	criteria provided, single submitter	clinical testing	This missense variant replaces glutamic acid with aspartic acid at codon 347 of the PMS2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with Lynch syndrome (PMID: 31350202). This variant has been identified in 11/251116 chromosomes 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.
Myriad Genetics, Inc.	RCV000411537	SCV004019980	uncertain significance	Lynch syndrome 4	2023-04-05	criteria provided, single submitter	clinical testing	This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
All of Us Research Program, National Institutes of Health	RCV003997283	SCV004839857	uncertain significance	Lynch syndrome	2023-11-09	criteria provided, single submitter	clinical testing	This missense variant replaces glutamic acid with aspartic acid at codon 347 of the PMS2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with Lynch syndrome (PMID: 31350202). This variant has been identified in 11/251116 chromosomes 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.