Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001188700 | SCV001355832 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-07 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with glutamic acid at codon 350 of the MUTYH protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MUTYH-related disorders in the literature. This variant has been identified in 1/246384 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Invitae | RCV002559155 | SCV003323987 | uncertain significance | Familial adenomatous polyposis 2 | 2022-11-24 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 926218). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 350 of the MUTYH protein (p.Asp350Glu). |
Ambry Genetics | RCV001188700 | SCV004055754 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-29 | criteria provided, single submitter | clinical testing | The p.D350E variant (also known as c.1050C>A), located in coding exon 12 of the MUTYH gene, results from a C to A substitution at nucleotide position 1050. The aspartic acid at codon 350 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Baylor Genetics | RCV002559155 | SCV004198955 | uncertain significance | Familial adenomatous polyposis 2 | 2023-05-12 | criteria provided, single submitter | clinical testing |