Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000132280 | SCV000187364 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-01 | criteria provided, single submitter | clinical testing | The p.R39P variant (also known as c.116G>C), located in coding exon 1 of the MSH2 gene, results from a G to C substitution at nucleotide position 116. The arginine at codon 39 is replaced by proline, an amino acid with dissimilar properties. This alteration, called a variant of uncertain significance, was detected in a cohort of 1058 colorectal cancer patients who underwent multi-gene panel testing (Yurgelun MB et al. J. Clin. Oncol., 2017 Apr;35:1086-1095). 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 01;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. |
| Color Diagnostics, |
RCV000132280 | SCV000908268 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-12 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000780435 | SCV000917683 | uncertain significance | not specified | 2018-01-24 | criteria provided, single submitter | clinical testing | Variant summary: The MSH2 c.116G>C (p.Arg39Pro) variant involves the alteration of a conserved nucleotide that leads to an amino acid substitution in the N-terminal mismatch-recognition domain (IPR007695, InterPro). 4/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 5/222394 control chromosomes at a frequency of 0.0000225, which does not exceed the estimated maximal expected allele frequency of a pathogenic MSH2 variant (0.0005683). The variant was reported in one individual with colorectal cancer, however without evidence for causality (Yurgelun 2017). In addition, one clinical diagnostic laboratory classified this variant as uncertain significance. Taken together, this variant is classified as VUS. |
| Invitae | RCV000800194 | SCV000939894 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2023-09-17 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001753517 | SCV001985746 | uncertain significance | not provided | 2023-01-19 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Observed in individuals with colorectal cancer (Yurgelun et al., 2017); This variant is associated with the following publications: (PMID: 21120944, 18822302, 28135145, 35713195) |
| Baylor Genetics | RCV003462042 | SCV004194539 | uncertain significance | Lynch syndrome 1 | 2023-06-22 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV003998140 | SCV004828892 | uncertain significance | Lynch syndrome | 2023-03-04 | criteria provided, single submitter | clinical testing |