ClinVar Miner

Submissions for variant NM_000214.3(JAG1):c.1393C>T (p.Arg465Trp)

dbSNP: rs937263997
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000728269 SCV000855822 uncertain significance not provided 2017-07-17 criteria provided, single submitter clinical testing
Invitae RCV001339960 SCV001533745 uncertain significance Alagille syndrome due to a JAG1 point mutation 2020-07-30 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 465 of the JAG1 protein (p.Arg465Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with JAG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 593274). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV002388358 SCV002697106 uncertain significance Cardiovascular phenotype 2022-03-12 criteria provided, single submitter clinical testing The p.R465W variant (also known as c.1393C>T), located in coding exon 11 of the JAG1 gene, results from a C to T substitution at nucleotide position 1393. The arginine at codon 465 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002507284 SCV002814967 uncertain significance Alagille syndrome due to a JAG1 point mutation; Tetralogy of Fallot; Deafness, congenital heart defects, and posterior embryotoxon; Charcot-Marie-Tooth disease, axonal, Type 2HH 2021-08-04 criteria provided, single submitter clinical testing

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