Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001052256 | SCV001216458 | uncertain significance | not provided | 2025-01-07 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 892 of the MSH3 protein (p.Met892Val). This variant is present in population databases (rs773713925, gnomAD 0.007%). This missense change has been observed in individual(s) with colon cancer (PMID: 29212164). ClinVar contains an entry for this variant (Variation ID: 848488). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
Ambry Genetics | RCV002429649 | SCV002741316 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-08-19 | criteria provided, single submitter | clinical testing | The p.M892V variant (also known as c.2674A>G), located in coding exon 20 of the MSH3 gene, results from an A to G substitution at nucleotide position 2674. The methionine at codon 892 is replaced by valine, an amino acid with highly similar properties. This alteration was reported in an individual with colorectal cancer diagnosed at age 74 and two first degree relatives who were also diagnosed with colon cancer (Raskin L et al. Oncotarget, 2017 Nov;8:93450-93463). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |
Baylor Genetics | RCV004570191 | SCV005054789 | uncertain significance | Endometrial carcinoma | 2023-11-22 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV005036343 | SCV005666210 | uncertain significance | Endometrial carcinoma; Familial adenomatous polyposis 4 | 2024-06-12 | criteria provided, single submitter | clinical testing |