Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000219830 | SCV000275466 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-24 | criteria provided, single submitter | clinical testing | The p.A385S variant (also known as c.1153G>T), located in coding exon 12 of the MUTYH gene, results from a G to T substitution at nucleotide position 1153. The alanine at codon 385 is replaced by serine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. 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. |
| Labcorp Genetics |
RCV000456233 | SCV000545797 | uncertain significance | Familial adenomatous polyposis 2 | 2024-04-24 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 385 of the MUTYH protein (p.Ala385Ser). 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 variant has not been reported in the literature in individuals affected with MUTYH-related conditions. ClinVar contains an entry for this variant (Variation ID: 231570). 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. |
| Prevention |
RCV000679423 | SCV000806336 | uncertain significance | not provided | 2017-10-05 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV000456233 | SCV004198916 | uncertain significance | Familial adenomatous polyposis 2 | 2024-03-08 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000219830 | SCV004358562 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-03 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with serine at codon 385 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 1/249808 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. |