Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001229815 | SCV001402272 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2022-08-16 | 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: 956924). 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 asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 45 of the PMS2 protein (p.Asn45Ser). |
Mendelics | RCV002249818 | SCV002519146 | uncertain significance | not specified | 2022-05-04 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002379879 | SCV002690306 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-05-15 | criteria provided, single submitter | clinical testing | The p.N45S variant (also known as c.134A>G), located in coding exon 2 of the PMS2 gene, results from an A to G substitution at nucleotide position 134. The asparagine at codon 45 is replaced by serine, an amino acid with highly similar properties. Another alteration at this same codon (p.A45T/c.134A>C) has been reported in the compound heterozygous state with a second PMS2 mutation in a patient with constitutional mismatch repair deficiency (CMMRD) (Lech B et al. Allergol Immunopathol (Madr);15:121-6). This amino acid position is highly 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. |