Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001216041 | SCV001387813 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-01-06 | 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 performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 33357406) indicates that this missense variant is not expected to disrupt MSH2 function. ClinVar contains an entry for this variant (Variation ID: 945408). This missense change has been observed in individual(s) with clinical features of MSH2-related conditions (PMID: 21520333). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 148 of the MSH2 protein (p.Val148Leu). |
| Ambry Genetics | RCV002327505 | SCV002628290 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-06-23 | criteria provided, single submitter | clinical testing | The p.V148L variant (also known as c.442G>C), located in coding exon 3 of the MSH2 gene, results from a G to C substitution at nucleotide position 442. The valine at codon 148 is replaced by leucine, 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. |