ClinVar Miner

Submissions for variant NM_001048174.2(MUTYH):c.761C>T (p.Ala254Val)

gnomAD frequency: 0.00001  dbSNP: rs587782764
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132291 SCV000187376 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-06 criteria provided, single submitter clinical testing The p.A282V variant (also known as c.845C>T), located in coding exon 10 of the MUTYH gene, results from a C to T substitution at nucleotide position 845. The alanine at codon 282 is replaced by valine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000476647 SCV000545788 uncertain significance Familial adenomatous polyposis 2 2024-01-28 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 282 of the MUTYH protein (p.Ala282Val). This variant is present in population databases (rs587782764, gnomAD 0.004%). 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: 142849). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Counsyl RCV000476647 SCV000788627 uncertain significance Familial adenomatous polyposis 2 2017-12-22 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000132291 SCV000905860 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-17 criteria provided, single submitter clinical testing This missense variant replaces alanine with valine at codon 282 of the MUTYH protein. This variant is also known as c.803C>T (p.Ala268Val) based on an alternative transcript (NM_001048171). 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 2/282074 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.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV000476647 SCV003928118 uncertain significance Familial adenomatous polyposis 2 2023-04-20 criteria provided, single submitter clinical testing The MUTYH c.845C>T (p.Ala282Val) missense change has a maximum subpopulation frequency of 0.004% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported in individuals with MUTYH-associated polyposis. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
All of Us Research Program, National Institutes of Health RCV000476647 SCV004843217 uncertain significance Familial adenomatous polyposis 2 2023-10-02 criteria provided, single submitter clinical testing This missense variant replaces alanine with valine at codon 282 of the MUTYH protein. This variant is also known as c.803C>T (p.Ala268Val) based on an alternative transcript (NM_001048171). Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 2/282074 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.
Baylor Genetics RCV000476647 SCV005056025 uncertain significance Familial adenomatous polyposis 2 2024-03-27 criteria provided, single submitter clinical testing

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