Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000213928 | SCV000277451 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-04-02 | criteria provided, single submitter | clinical testing | The p.A36S variant (also known as c.106G>T), located in coding exon 1 of the MSH6 gene, results from a G to T substitution at nucleotide position 106. The alanine at codon 36 is replaced by serine, an amino acid with similar properties. In one study, this alteration was detected in a Spanish endometrial cancer patient whose tumor demonstrated microsatellite instability and loss of MSH2 and MSH6 expression on IHC (Rubio I et al. Oncology, 2016 Jul;91:171-6). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV002515699 | SCV003306991 | benign | Hereditary nonpolyposis colorectal neoplasms | 2022-03-17 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003477754 | SCV004221133 | uncertain significance | not provided | 2023-07-21 | criteria provided, single submitter | clinical testing | In the published literature, this variant has been reported in an individual with endometrial cancer (PMID: 27398995 (2016)). The frequency of this variant in the general population, 0.0000043 (1/234488 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |