Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000131452 | SCV000186436 | likely benign | Hereditary cancer-predisposing syndrome | 2018-09-05 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Color Diagnostics, |
RCV000131452 | SCV000905868 | likely benign | Hereditary cancer-predisposing syndrome | 2017-02-28 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000824066 | SCV000964947 | uncertain significance | Familial adenomatous polyposis 2 | 2023-12-27 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 42 of the MUTYH protein (p.Asn42Ser). This variant is present in population databases (rs563275223, gnomAD 0.02%). This missense change has been observed in individual(s) with familial adenomatous polyposis (PMID: 23460355). ClinVar contains an entry for this variant (Variation ID: 142369). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001194163 | SCV001363475 | uncertain significance | not specified | 2019-06-17 | criteria provided, single submitter | clinical testing | Variant summary: MUTYH c.125A>G (p.Asn42Ser) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 251488 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.125A>G has been reported in the literature in one individual affected with MUTYH-associated Polyposis (Cruz-Correa_2013). This report does not provide unequivocal conclusions about association of the variant with MUTYH-associated Polyposis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance. |