Submissions for variant NM_000214.3(JAG1):c.73C>T (p.Arg25Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV005103636	SCV005837945	pathogenic	Alagille syndrome due to a JAG1 point mutation	2024-07-17	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg25*) in the JAG1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in JAG1 are known to be pathogenic (PMID: 11180599). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Alagille syndrome (PMID: 10220506, 35595280). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences	RCV004729915	SCV005337025	pathogenic	JAG1-related disorder	2024-07-11	no assertion criteria provided	clinical testing	The JAG1 c.73C>T variant is predicted to result in premature protein termination (p.Arg25*). This variant was reported in an individual with Alagille syndrome (Crosnier et al. 1999. PubMed ID: 10220506; Table S1, Wang H et al 2022. PubMed ID: 35595280). This variant has not been reported in a large population database, indicating this variant is rare. Nonsense variants in JAG1 are expected to be pathogenic. This variant is interpreted as pathogenic.