Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000164470 | SCV000215114 | uncertain significance | Hereditary cancer-predisposing syndrome | 2014-06-09 | criteria provided, single submitter | clinical testing | The p.V5L variant (also known as c.13G>C), located in coding exon 1 of the MUTYH gene, results from a G to C substitution at nucleotide position 13. The valine at codon 5 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 6502 samples (13004 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.005% (greater than 21000 alleles tested) in our clinical cohort (includes this individual). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be benign and tolerated by PolyPhen and SIFT in silico analyses, respectively. Since supporting evidence is limited at this time, the clinical significance of p.V5L remains unclear. |
| Invitae | RCV001850298 | SCV002255281 | uncertain significance | Familial adenomatous polyposis 2 | 2021-02-14 | criteria provided, single submitter | clinical testing | 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 and their clinical significance is uncertain. 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. This variant has not been reported in the literature in individuals with MUTYH-related conditions. ClinVar contains an entry for this variant (Variation ID: 185106). This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with leucine at codon 5 of the MUTYH protein (p.Val5Leu). The valine residue is weakly conserved and there is a small physicochemical difference between valine and leucine. |