Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000131405 | SCV000186381 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-02-21 | criteria provided, single submitter | clinical testing | The p.M351I variant (also known as c.1053G>C), located in coding exon 6 of the MSH2 gene, results from a G to C substitution at nucleotide position 1053. The methionine at codon 351 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. In addition, this alteration is predicted to be benign by MAPP-MMR in silico analyses (Chao EC et al. Hum. Mutat. 2008 Jun;29:852-60). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV000552818 | SCV000625222 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2019-07-20 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with isoleucine at codon 351 of the MSH2 protein (p.Met351Ile). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and isoleucine. This variant is present in population databases (rs373122667, ExAC 0.001%) but has not been reported in the literature in individuals with a MSH2-related disease. ClinVar contains an entry for this variant (Variation ID: 142335). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Color | RCV000131405 | SCV000684900 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-12 | criteria provided, single submitter | clinical testing |