Submissions for variant NM_000214.3(JAG1):c.473C>T (p.Ser158Leu)

dbSNP: rs747203032

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003620202	SCV004530166	uncertain significance	Alagille syndrome due to a JAG1 point mutation	2023-10-09	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 158 of the JAG1 protein (p.Ser158Leu). This variant is present in population databases (rs747203032, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with JAG1-related conditions. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on JAG1 protein function. 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.
PreventionGenetics, part of Exact Sciences	RCV004554309	SCV004796801	uncertain significance	JAG1-related disorder	2024-02-29	no assertion criteria provided	clinical testing	The JAG1 c.473C>T variant is predicted to result in the amino acid substitution p.Ser158Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.