Submissions for variant NM_206937.2(LIG4):c.1942A>C (p.Asn648His)

gnomAD frequency: 0.00001  dbSNP: rs1271457786

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002013215	SCV002295853	uncertain significance	DNA ligase IV deficiency	2023-07-07	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) 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 LIG4 protein function. ClinVar contains an entry for this variant (Variation ID: 1500019). This variant has not been reported in the literature in individuals affected with LIG4-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 648 of the LIG4 protein (p.Asn648His).