Submissions for variant NM_017617.5(NOTCH1):c.4879C>T (p.Arg1627Cys)

dbSNP: rs1203442527

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000520423	SCV000621143	uncertain significance	not provided	2017-09-21	criteria provided, single submitter	clinical testing	The R1627C variant in the NOTCH1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R1627C variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R1627C 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. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret R1627C as a variant of uncertain significance
Ambry Genetics	RCV004822087	SCV005456740	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2024-11-19	criteria provided, single submitter	clinical testing	The p.R1627C variant (also known as c.4879C>T), located in coding exon 26 of the NOTCH1 gene, results from a C to T substitution at nucleotide position 4879. The arginine at codon 1627 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.