ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.4066C>T (p.Arg1356Cys) (rs587778567)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000658393 SCV000780165 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 R1356C variant has been published in one European individual from a cohort of individuals with no known personal or family history indicative of a cancer predisposition syndrome who underwent whole genome sequencing (Bodian et al., 2014), although additional clinical details unrelated to cancer history were not described. The R1356C variant is also not observed in large population cohorts (Lek et al., 2016). The R1356C 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. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. However, this variant has not been observed in a significant number of affected individuals, and it lacks both segregation and functional studies which would further clarify its pathogenicity.
ITMI RCV000121683 SCV000085881 not provided not specified 2013-09-19 no assertion provided reference population

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