Submissions for variant NM_017617.5(NOTCH1):c.5008G>T (p.Asp1670Tyr)

gnomAD frequency: 0.00001  dbSNP: rs1157456139

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002343086	SCV002640764	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2022-02-08	criteria provided, single submitter	clinical testing	The p.D1670Y variant (also known as c.5008G>T), located in coding exon 26 of the NOTCH1 gene, results from a G to T substitution at nucleotide position 5008. The aspartic acid at codon 1670 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx	RCV004784052	SCV005396079	uncertain significance	not provided	2024-05-08	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.