ClinVar Miner

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

gnomAD frequency: 0.00001  dbSNP: rs587778567
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Total submissions: 6
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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.
Invitae RCV001201674 SCV001372756 likely benign Adams-Oliver syndrome 5 2023-05-15 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001201674 SCV002553439 uncertain significance Adams-Oliver syndrome 5 2022-03-15 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002269858 SCV002553440 uncertain significance Aortic valve disease 1 2022-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV004019690 SCV004990173 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2021-12-30 criteria provided, single submitter clinical testing The c.4066C>T (p.R1356C) alteration is located in exon 25 (coding exon 25) of the NOTCH1 gene. This alteration results from a C to T substitution at nucleotide position 4066, causing the arginine (R) at amino acid position 1356 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
ITMI RCV000121683 SCV000085881 not provided not specified 2013-09-19 no assertion provided reference population

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