Submissions for variant NM_017617.5(NOTCH1):c.7298T>C (p.Phe2433Ser)

gnomAD frequency: 0.00020  dbSNP: rs201493851

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000822987	SCV000963819	likely benign	Adams-Oliver syndrome 5	2024-11-11	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004029121	SCV003693406	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2021-07-14	criteria provided, single submitter	clinical testing	The c.7298T>C (p.F2433S) alteration is located in exon 34 (coding exon 34) of the NOTCH1 gene. This alteration results from a T to C substitution at nucleotide position 7298, causing the phenylalanine (F) at amino acid position 2433 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx	RCV004721639	SCV005328054	uncertain significance	not provided	2024-02-28	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
PreventionGenetics, part of Exact Sciences	RCV004735822	SCV005351868	likely benign	NOTCH1-related disorder	2024-06-10	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).