ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1103A>G (p.Asn368Ser)

gnomAD frequency: 0.00002  dbSNP: rs777814445
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000205079 SCV000259374 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2024-09-24 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 368 of the PMS2 protein (p.Asn368Ser). This variant is present in population databases (rs777814445, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 219486). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt PMS2 protein function with a negative predictive value of 80%. 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.
GeneDx RCV000479052 SCV000565395 uncertain significance not provided 2024-03-20 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 35534704)
Color Diagnostics, LLC DBA Color Health RCV000584467 SCV000690996 uncertain significance Hereditary cancer-predisposing syndrome 2023-11-20 criteria provided, single submitter clinical testing This missense variant replaces asparagine with serine at codon 368 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 not been reported in individuals affected with PMS2-related disorders in the literature. This variant has been identified in 6/251292 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.
Ambry Genetics RCV000584467 SCV001178385 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-22 criteria provided, single submitter clinical testing The p.N368S variant (also known as c.1103A>G), located in coding exon 10 of the PMS2 gene, results from an A to G substitution at nucleotide position 1103. The asparagine at codon 368 is replaced by serine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV004567451 SCV005056378 uncertain significance Lynch syndrome 4 2024-03-29 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004806197 SCV005429603 uncertain significance Lynch syndrome 2024-06-09 criteria provided, single submitter clinical testing This missense variant replaces asparagine with serine at codon 368 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 not been reported in individuals affected with PMS2-related disorders in the literature. This variant has been identified in 6/251292 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.
Fulgent Genetics, Fulgent Genetics RCV005042438 SCV005674333 uncertain significance Lynch syndrome 4; Mismatch repair cancer syndrome 4 2024-03-10 criteria provided, single submitter clinical testing

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