Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000580400 | SCV000685111 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-08-29 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000580400 | SCV001187355 | likely benign | Hereditary cancer-predisposing syndrome | 2023-07-07 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Labcorp Genetics |
RCV002529101 | SCV003487531 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2024-02-02 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 213 of the MSH2 protein (p.Leu213Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with ovarian cancer (PMID: 34326862). ClinVar contains an entry for this variant (Variation ID: 489949). 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. |
| Department of Pathology and Laboratory Medicine, |
RCV001356461 | SCV001551638 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The MSH2 p.L213Q variant was not identified in the literature nor was it identified in dbSNP or COSMIC. The variant was identified in ClinVar (classified as uncertain significance by Ambry Genetics and Color) but was not identified in the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, or the Genome Aggregation Database (March 6, 2019, v2.1.1). The p.L213 residue is conserved in mammals and more distantly related organisms, and computational analyses (MUT Assesor, PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a deleterious effect on splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |