ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.5560C>T (p.Arg1854Cys)

gnomAD frequency: 0.00001  dbSNP: rs376689092
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002315123 SCV000739491 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-01-21 criteria provided, single submitter clinical testing The p.R1854C variant (also known as c.5560C>T), located in coding exon 30 of the NOTCH1 gene, results from a C to T substitution at nucleotide position 5560. The arginine at codon 1854 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000814127 SCV000954527 likely benign Adams-Oliver syndrome 5 2023-08-01 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000825407 SCV000966704 uncertain significance not specified 2018-10-24 criteria provided, single submitter clinical testing The p.Arg1854Cys variant in NOTCH1 has not been reported in the literature in in dividuals with aortic valve disease or Adams-Oliver syndrome, but has been repor ted as a variant of uncertain signficance in ClinVar (Variation ID# 520079). It has also been identified in 0.01% (3/23838) of African chromosomes by gnomAD (ht tp://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis suggest that the variant may impact the protein, though this informati on is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Arg1854Cys variant is uncertain. ACMG/AMP Criteria applie d: PM2_Supporting, PP3.
Genome-Nilou Lab RCV000814127 SCV002553335 uncertain significance Adams-Oliver syndrome 5 2022-03-15 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002270911 SCV002553337 uncertain significance Aortic valve disease 1 2022-03-15 criteria provided, single submitter clinical testing
GeneDx RCV005091792 SCV005848280 uncertain significance not provided 2024-08-12 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26699486)

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