Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000570606 | SCV000676086 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-15 | criteria provided, single submitter | clinical testing | The p.I511M variant (also known as c.1533T>G), located in coding exon 10 of the MSH2 gene, results from a T to G substitution at nucleotide position 1533. The isoleucine at codon 511 is replaced by methionine, 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. |
| Color Diagnostics, |
RCV000570606 | SCV001359084 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-04 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with methionine at codon 511 of the MSH2 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). 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. |
| Labcorp Genetics |
RCV001297040 | SCV001486023 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-12-22 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 511 of the MSH2 protein (p.Ile511Met). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MSH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 486876). 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 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. |
| Baylor Genetics | RCV003459408 | SCV004194550 | uncertain significance | Lynch syndrome 1 | 2023-06-13 | criteria provided, single submitter | clinical testing |