ClinVar Miner

Submissions for variant NM_000214.3(JAG1):c.551G>A (p.Arg184His) (rs121918351)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000725979 SCV000340966 pathogenic not provided 2017-04-07 criteria provided, single submitter clinical testing
Invitae RCV000008059 SCV000829372 pathogenic Alagille syndrome 1 2018-05-14 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 184 of the JAG1 protein (p.Arg184His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with Alagille syndrome (PMID: 9585603, 10220506, 12442286, 24748328, 25676721). ClinVar contains an entry for this variant (Variation ID: 7620). Experimental studies have shown that this missense change results in a JAG1 protein that does not traffic to the cell membrane and loses its transactivation capabilities (PMID: 11058898, 22487239). The p.Arg184 amino acid residue in JAG1 has been determined to be clinically significant (PMID: 10533065, 10220506). This suggests that variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000763445 SCV000894216 pathogenic Alagille syndrome 1; Tetralogy of Fallot; Deafness, congenital heart defects, and posterior embryotoxon 2018-10-31 criteria provided, single submitter clinical testing
OMIM RCV000008059 SCV000028264 pathogenic Alagille syndrome 1 2001-02-15 no assertion criteria provided literature only
GeneReviews RCV000008059 SCV001167335 pathogenic Alagille syndrome 1 2019-12-04 no assertion criteria provided literature only

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