Submissions for variant NM_017617.5(NOTCH1):c.6895G>A (p.Gly2299Ser)

gnomAD frequency: 0.00001  dbSNP: rs1020747496

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000521367	SCV000622002	uncertain significance	not provided	2017-11-02	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the NOTCH1 gene. The G2299S variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The G2299S 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 addition, this substitution occurs at a position that is conserved across species. Nevertheless, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000552480	SCV000659486	likely benign	Adams-Oliver syndrome 5	2025-01-29	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000552480	SCV002553272	uncertain significance	Adams-Oliver syndrome 5	2022-03-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002270636	SCV002553273	uncertain significance	Aortic valve disease 1	2022-03-15	criteria provided, single submitter	clinical testing