Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000218057 | SCV000276032 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-06-17 | criteria provided, single submitter | clinical testing | The p.P334T variant (also known as c.1000C>A), located in coding exon 12 of the MUTYH gene, results from a C to A substitution at nucleotide position 1000. The proline at codon 334 is replaced by threonine, an amino acid with highly 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. |
Counsyl | RCV000411238 | SCV000487382 | uncertain significance | Familial adenomatous polyposis 2 | 2016-10-13 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000411238 | SCV000545796 | uncertain significance | Familial adenomatous polyposis 2 | 2023-11-20 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 334 of the MUTYH protein (p.Pro334Thr). This variant is present in population databases (rs587778537, gnomAD 0.02%). 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: 134861). An algorithm developed specifically for the MUTYH gene suggests that this missense change is likely to be deleterious (PMID: 23621914). 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. |
Color Diagnostics, |
RCV000218057 | SCV000903810 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-01 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with threonine at codon 334 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 7/228910 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. |
Gene |
RCV001576763 | SCV001804015 | uncertain significance | not provided | 2024-01-18 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Identified in healthy individuals undergoing whole genome sequencing (PMID: 24728327); This variant is associated with the following publications: (PMID: 24470512, 16879101, 20816984, 24728327) |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001576763 | SCV004222068 | uncertain significance | not provided | 2023-08-09 | criteria provided, single submitter | clinical testing | This variant has not been reported in the published literature. The frequency of this variant in the general population, 0.00019 (6/32216 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
All of Us Research Program, |
RCV000411238 | SCV004835170 | uncertain significance | Familial adenomatous polyposis 2 | 2023-10-02 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with threonine at codon 334 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 7/228910 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. |
ITMI | RCV000121594 | SCV000085790 | not provided | not specified | 2013-09-19 | no assertion provided | reference population |