Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001062944 | SCV001227770 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-10-17 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 123 of the MSH2 protein (p.Ala123Thr). This variant is present in population databases (rs768313992, gnomAD 0.0009%). This missense change has been observed in individual(s) with ovarian cancer (PMID: 36169650). ClinVar contains an entry for this variant (Variation ID: 857301). 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 | RCV002451268 | SCV002615881 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-02-14 | criteria provided, single submitter | clinical testing | The p.A123T variant (also known as c.367G>A) is located in coding exon 3 of the MSH2 gene. The alanine at codon 123 is replaced by threonine, an amino acid with similar properties. This change occurs in the first base pair of coding exon 3. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. In addition, this alteration is predicted to be borderline deleterious by MAPP-MMR in silico analyses (Chao EC et al. Hum. Mutat. 2008 Jun;29:852-60). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |