Submissions for variant NM_024408.4(NOTCH2):c.3912C>T (p.Phe1304=)

gnomAD frequency: 0.00007  dbSNP: rs764301517

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002094687	SCV002388066	likely benign	Hajdu-Cheney syndrome	2021-07-28	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002494171	SCV002795135	likely benign	Alagille syndrome due to a NOTCH2 point mutation; Hajdu-Cheney syndrome	2021-12-27	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004741219	SCV005360742	uncertain significance	NOTCH2-related disorder	2024-07-31	no assertion criteria provided	clinical testing	The NOTCH2 c.3912C>T variant is not predicted to result in an amino acid change (p.=). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.021% of alleles in individuals of African descent in gnomAD. This variant is predicted to alter splicing based on available splicing prediction software (SpliceAI, Jaganathan et al. 2019. PubMed ID: 30661751). However, the use of computer prediction softwares is not equivalent to functional evidence. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.