ClinVar Miner

Submissions for variant NM_001128425.1(MUTYH):c.718G>A (p.Ala240Thr) (rs774237159)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000468855 SCV000545787 uncertain significance MYH-associated polyposis 2020-10-08 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 240 of the MUTYH protein (p.Ala240Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs774237159, ExAC 0.003%). This variant has not been reported in the literature in individuals with MUTYH-related disease. ClinVar contains an entry for this variant (Variation ID: 406859). 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 threonine 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Ambry Genetics RCV000565823 SCV000662643 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-28 criteria provided, single submitter clinical testing The p.A240T variant (also known as c.718G>A), located in coding exon 9 of the MUTYH gene, results from a G to A substitution at nucleotide position 718. The alanine at codon 240 is replaced by threonine, an amino acid with similar properties. 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.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001356323 SCV001551458 uncertain significance not provided no assertion criteria provided clinical testing

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