ClinVar Miner

Submissions for variant NM_000214.3(JAG1):c.2998A>G (p.Ile1000Val)

gnomAD frequency: 0.00001  dbSNP: rs773974344
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000732743 SCV000860727 uncertain significance not provided 2018-04-06 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001138544 SCV001298605 uncertain significance Isolated Nonsyndromic Congenital Heart Disease 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Invitae RCV001855693 SCV002215774 uncertain significance Alagille syndrome due to a JAG1 point mutation 2021-10-13 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt JAG1 protein function. ClinVar contains an entry for this variant (Variation ID: 596796). This variant has not been reported in the literature in individuals affected with JAG1-related conditions. This variant is present in population databases (rs773974344, ExAC 0.004%). This sequence change replaces isoleucine with valine at codon 1000 of the JAG1 protein (p.Ile1000Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine.
Ambry Genetics RCV002440574 SCV002746958 uncertain significance Cardiovascular phenotype 2018-02-27 criteria provided, single submitter clinical testing The p.I1000V variant (also known as c.2998A>G), located in coding exon 24 of the JAG1 gene, results from an A to G substitution at nucleotide position 2998. The isoleucine at codon 1000 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. 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 RCV002493345 SCV002785340 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 2021-08-23 criteria provided, single submitter clinical testing

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