ClinVar Miner

Submissions for variant NM_000214.3(JAG1):c.448A>G (p.Ser150Gly)

gnomAD frequency: 0.00001  dbSNP: rs1229047867
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001753392 SCV002005006 uncertain significance not provided 2019-08-09 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002329742 SCV002635361 uncertain significance Cardiovascular phenotype 2021-09-20 criteria provided, single submitter clinical testing The p.S150G variant (also known as c.448A>G), located in coding exon 4 of the JAG1 gene, results from an A to G substitution at nucleotide position 448. The serine at codon 150 is replaced by glycine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV005023249 SCV005656345 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 2024-02-29 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV005095087 SCV005808528 uncertain significance Alagille syndrome due to a JAG1 point mutation 2024-02-17 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 150 of the JAG1 protein (p.Ser150Gly). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with JAG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1318845). 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 with a negative predictive value of 95%. 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.

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