Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001177172 | SCV001341344 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-28 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with alanine at codon 807 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). This variant does not impact MSH2 function in a 6-thioguanine sensitivity assay in haploid human cells (internally defined LOF score threshold <= -1.32, PMID: 33357406). This variant has not 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). 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. |
Invitae | RCV001875836 | SCV002168608 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2021-07-03 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with alanine at codon 807 of the MSH2 protein (p.Thr807Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine. This variant has not been reported in the literature in individuals affected with MSH2-related conditions. 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 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. ClinVar contains an entry for this variant (Variation ID: 919163). |
Ambry Genetics | RCV001177172 | SCV002732841 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-04 | criteria provided, single submitter | clinical testing | The p.T807A variant (also known as c.2419A>G), located in coding exon 14 of the MSH2 gene, results from an A to G substitution at nucleotide position 2419. The threonine at codon 807 is replaced by alanine, 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. |
All of Us Research Program, |
RCV004006371 | SCV004834183 | uncertain significance | Lynch syndrome | 2023-07-19 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with alanine at codon 807 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). This variant does not impact MSH2 function in a 6-thioguanine sensitivity assay in haploid human cells (internally defined LOF score threshold <= -1.32, PMID: 33357406). This variant has not 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). 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. |