Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000568035 | SCV000662606 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-28 | criteria provided, single submitter | clinical testing | The p.L101V variant (also known as c.301C>G), located in coding exon 3 of the MUTYH gene, results from a C to G substitution at nucleotide position 301. The leucine at codon 101 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to create a new alternate splice donor site; however, direct evidence is unavailable. 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. |
| Labcorp Genetics |
RCV001858115 | SCV002259198 | uncertain significance | Familial adenomatous polyposis 2 | 2020-11-26 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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"). This variant has not been reported in the literature in individuals with MUTYH-related conditions. ClinVar contains an entry for this variant (Variation ID: 479984). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces leucine with valine at codon 101 of the MUTYH protein (p.Leu101Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. |