Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV003221187 | SCV003913559 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-19 | criteria provided, single submitter | clinical testing | The p.D742H variant (also known as c.2224G>C), located in coding exon 14 of the MSH2 gene, results from a G to C substitution at nucleotide position 2224. The aspartic acid at codon 742 is replaced by histidine, an amino acid with 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 deleterious neutral (Jia X et al. Am J Hum Genet, 2021 Jan;108:163-175). 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, |
RCV004009672 | SCV004842916 | uncertain significance | Lynch syndrome | 2023-11-30 | criteria provided, single submitter | clinical testing |