ClinVar Miner

Submissions for variant NM_001048174.2(MUTYH):c.1193G>T (p.Arg398Leu)

dbSNP: rs748700385
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000219054 SCV000278437 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-22 criteria provided, single submitter clinical testing The p.R426L variant (also known as c.1277G>T), located in coding exon 13 of the MUTYH gene, results from a G to T substitution at nucleotide position 1277. The arginine at codon 426 is replaced by leucine, an amino acid with dissimilar properties. This variant was reported in 2/60,466 breast cancer cases and in 0/53,461 controls (Dorling et al. N Engl J Med. 2021 02;384:428-439). This amino acid position is poorly 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 (formerly Invitae), Labcorp RCV000233765 SCV000285922 uncertain significance Familial adenomatous polyposis 2 2024-01-30 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 426 of the MUTYH protein (p.Arg426Leu). This variant is present in population databases (rs748700385, gnomAD 0.003%). 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: 233962). 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 RCV000233765 SCV000487373 uncertain significance Familial adenomatous polyposis 2 2016-08-02 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000219054 SCV000685561 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-02 criteria provided, single submitter clinical testing This missense variant replaces arginine with leucine at codon 426 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 performed for this variant. In a large international case-control study, this variant was reported in 2/60466 breast cancer cases and absent in 53461 controls (PMID: 33471991). This variant has been identified in 1/251262 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.

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