ClinVar Miner

Submissions for variant NM_001128425.1(MUTYH):c.1622C>T (p.Ala541Val) (rs751053826)

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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 RCV000164546 SCV000215202 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-28 criteria provided, single submitter clinical testing The p.A541V variant (also known as c.1622C>T), located in coding exon 16 of the MUTYH gene, results from a C to T substitution at nucleotide position 1622. The alanine at codon 541 is replaced by valine, an amino acid with 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.
Invitae RCV000474274 SCV000545805 uncertain significance MYH-associated polyposis 2020-09-30 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 541 of the MUTYH protein (p.Ala541Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs751053826, ExAC 0.001%). This variant has not been reported in the literature in individuals with MUTYH-related disease. ClinVar contains an entry for this variant (Variation ID: 185177). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C0. The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589735 SCV000697689 uncertain significance not provided 2016-10-21 criteria provided, single submitter clinical testing Variant summary: The c.1622C>T (p.Ala541Val) in MUTYH gene is a missense change that involves a non-conserved nucleotide and 3/5 in silico tools predict benign outcome. The variant of interest is located outside of any known functional domain, although the functional impact of this missense change is yet to be studied. The variant is present in the large control population dataset of ExAC at a frequency 0.000008 (1/121410 chrs tested), which does not exceed the maximal expected frequency of a pathogenic allele (0.0056) in this gene. The variant has not been reported, to our knowledge, in affected individuals via published reports. In addition, it was cited as VUS by a reputable database/clinical laboratory. Taken together, the variant has been classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available.
Color Health, Inc RCV000164546 SCV000903806 uncertain significance Hereditary cancer-predisposing syndrome 2020-01-02 criteria provided, single submitter clinical testing

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