Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000630129 | SCV000751085 | benign | Hereditary nonpolyposis colorectal neoplasms | 2023-11-28 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV001024658 | SCV001186713 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-13 | criteria provided, single submitter | clinical testing | The p.D197H variant (also known as c.589G>C), located in coding exon 3 of the MSH6 gene, results from a G to C substitution at nucleotide position 589. The aspartic acid at codon 197 is replaced by histidine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. In addition, the CoDP in silico tool predicts this alteration to have minor impact on molecular function, with a score of 0.001 (Terui H et al. J. Biomed. Sci. 2013 Apr;20:25). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV002483771 | SCV002790154 | uncertain significance | Endometrial carcinoma; Lynch syndrome 5; Mismatch repair cancer syndrome 3 | 2021-11-08 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV004002791 | SCV004841071 | uncertain significance | Lynch syndrome | 2023-05-30 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with histidine at codon 197 of the MSH6 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 not been reported in individuals affected with MSH6-related disorders in the literature. This variant has been identified in 1/251398 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. |