ClinVar Miner

Submissions for variant NM_001128425.2(MUTYH):c.10C>T (p.Leu4Phe)

dbSNP: rs587782404
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000772839 SCV000906221 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-04 criteria provided, single submitter clinical testing This missense variant replaces leucine with phenylalanine at codon 4 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 1/249218 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 RCV000804149 SCV000944045 uncertain significance Familial adenomatous polyposis 2 2023-05-22 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 4 of the MUTYH protein (p.Leu4Phe). This variant is present in population databases (no rsID available, gnomAD 0.006%). 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. 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. ClinVar contains an entry for this variant (Variation ID: 628380). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions.
Ambry Genetics RCV000772839 SCV002741790 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-19 criteria provided, single submitter clinical testing The p.L4F variant (also known as c.10C>T), located in coding exon 1 of the MUTYH gene, results from a C to T substitution at nucleotide position 10. The leucine at codon 4 is replaced by phenylalanine, 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003387926 SCV004099696 uncertain significance not specified 2023-09-01 criteria provided, single submitter clinical testing
Baylor Genetics RCV000804149 SCV004198950 uncertain significance Familial adenomatous polyposis 2 2023-05-18 criteria provided, single submitter clinical testing

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