Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000629895 | SCV000750851 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-10-10 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 773 of the MSH2 protein (p.Lys773Asn). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 525694). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MSH2 protein function. 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 | RCV001015167 | SCV001175975 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-09 | criteria provided, single submitter | clinical testing | The p.K773N variant (also known as c.2319G>C), located in coding exon 14 of the MSH2 gene, results from a G to C substitution at nucleotide position 2319. The lysine at codon 773 is replaced by asparagine, an amino acid with similar properties. This amino acid position is not 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, |
RCV001015167 | SCV001357243 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-05 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with asparagine at codon 773 of the MSH2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with soft-tissue sarcoma (PMID: 32447321). This variant has been identified in 2/251432 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The 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. |
Sema4, |
RCV001015167 | SCV002534467 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-12 | criteria provided, single submitter | curation | |
All of Us Research Program, |
RCV004002779 | SCV004825869 | uncertain significance | Lynch syndrome | 2023-12-13 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with asparagine at codon 773 of the MSH2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with soft-tissue sarcoma (PMID: 32447321). This variant has been identified in 2/251432 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The 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. |