ClinVar Miner

Submissions for variant NM_001128425.1(MUTYH):c.268G>A (p.Val90Ile) (rs375526246)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000123148 SCV000166451 uncertain significance MYH-associated polyposis 2020-04-10 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 90 of the MUTYH protein (p.Val90Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs375526246, 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: 135985). 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 isoleucine 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 is not likely to affect RNA splicing, 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 RCV000213878 SCV000274886 likely benign Hereditary cancer-predisposing syndrome 2019-03-16 criteria provided, single submitter clinical testing In silico models in agreement (benign) ;Other strong data
Color Health, Inc RCV000213878 SCV000911728 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-08 criteria provided, single submitter clinical testing

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