ClinVar Miner

Submissions for variant NM_001048174.2(MUTYH):c.1015C>G (p.Pro339Ala)

gnomAD frequency: 0.00001  dbSNP: rs876660262
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000215104 SCV000277537 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-29 criteria provided, single submitter clinical testing The p.P367A variant (also known as c.1099C>G), located in coding exon 12 of the MUTYH gene, results from a C to G substitution at nucleotide position 1099. The proline at codon 367 is replaced by alanine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000557362 SCV000639251 uncertain significance Familial adenomatous polyposis 2 2025-01-21 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 367 of the MUTYH protein (p.Pro367Ala). This variant is present in population databases (no rsID available, gnomAD 0.002%). 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: 233206). 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.
Color Diagnostics, LLC DBA Color Health RCV000215104 SCV000911436 uncertain significance Hereditary cancer-predisposing syndrome 2022-08-22 criteria provided, single submitter clinical testing This missense variant replaces proline with alanine at codon 367 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 hereditary cancer in the literature. This variant has been identified in 4/281606 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.
PreventionGenetics, part of Exact Sciences RCV004532804 SCV004118569 uncertain significance MUTYH-related disorder 2023-05-25 criteria provided, single submitter clinical testing The MUTYH c.1099C>G variant is predicted to result in the amino acid substitution p.Pro367Ala. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0023% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-45797420-G-C). This variant is classified as uncertain in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/233206/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
All of Us Research Program, National Institutes of Health RCV000557362 SCV004838911 uncertain significance Familial adenomatous polyposis 2 2023-07-10 criteria provided, single submitter clinical testing This missense variant replaces proline with alanine at codon 367 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 hereditary cancer in the literature. This variant has been identified in 4/281606 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 RCV000557362 SCV005056061 uncertain significance Familial adenomatous polyposis 2 2024-01-25 criteria provided, single submitter clinical testing

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