ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.3262G>C (p.Gly1088Arg) (rs531420022)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000657938 SCV000779707 uncertain significance not provided 2018-05-31 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the NOTCH1 gene. The G1088R variant has not been published as pathogenic or been reported as benign to our knowledge. It has been observed in one other individual with cardiac abnormalities referred for genetic testing at GeneDx, although this individual also harbored a variant in a different gene and no informative segregation data are available. This variant is also not observed at a significant frequency in large population cohorts (Lek et al., 2016). The G1088R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, in-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Nevertheless, this variant has not been observed in a significant number of affected individuals, and it lacks both large segregation studies and functional evidence which would further clarify its pathogenicity..

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