Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000569034 | SCV000666470 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-02-09 | criteria provided, single submitter | clinical testing | The p.M153L variant (also known as c.457A>T), located in coding exon 5 of the MUTYH gene, results from an A to T substitution at nucleotide position 457. The methionine at codon 153 is replaced by leucine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 140000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. In addition, this amino acid alteration is predicted to be possibly damaging yet tolerated by PolyPhen and SIFT in silico analyses, respectively. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the nearby native splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Gene |
RCV001770511 | SCV002001256 | uncertain significance | not provided | 2020-12-16 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Labcorp Genetics |
RCV002298675 | SCV002590291 | uncertain significance | Familial adenomatous polyposis 2 | 2022-08-08 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 481799). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 153 of the MUTYH protein (p.Met153Leu). |