Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000167351 | SCV000218203 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-20 | criteria provided, single submitter | clinical testing | The p.R389Q variant (also known as c.1166G>A), located in coding exon 7 of the MSH2 gene, results from a G to A substitution at nucleotide position 1166. The arginine at codon 389 is replaced by glutamine, an amino acid with highly similar properties. In a massively parallel cell-based functional assay testing susceptibility to a DNA damaging agent, 6-thioguanine (6-TG), this variant was reported to be functionally neutral (Jia X et al. Am J Hum Genet, 2021 Jan;108:163-175). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV000629828 | SCV000750784 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2025-01-12 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000167351 | SCV001736140 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-12-15 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with glutamine at codon 389 of the MSH2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 5/251456 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. |
| Gene |
RCV003329248 | SCV004036940 | uncertain significance | not provided | 2023-09-18 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in an individual with inflammatory bowel disease-associated colorectal cancer (Biscaglia et al. 2021); This variant is associated with the following publications: (PMID: 27300758, 34347074, 36073783, 18822302, 21120944, 26648449) |
| St. |
RCV003444210 | SCV004171495 | uncertain significance | Lynch syndrome 1 | 2023-10-18 | criteria provided, single submitter | clinical testing | The MSH2 c.1530G>C (p.Gln510His) missense change has a maximum subpopulation frequency of 0.016% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). TThe in silico tool REVEL predicts a deleterious effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. This variant has been reported in the literature in an individual with characteristic features of Lynch syndrome (PMID: 26648449), and an individual with colorectal cancer (PMID: 27300758). In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |
| Baylor Genetics | RCV003444210 | SCV005053449 | uncertain significance | Lynch syndrome 1 | 2024-02-25 | criteria provided, single submitter | clinical testing |