ClinVar Miner

Submissions for variant NM_206937.2(LIG4):c.847A>G (p.Lys283Glu)

dbSNP: rs1594462950
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire, Universite Libre de Bruxelles RCV001007660 SCV000998522 likely pathogenic DNA ligase IV deficiency criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001007660 SCV004538961 likely pathogenic DNA ligase IV deficiency 2022-10-23 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 283 of the LIG4 protein (p.Lys283Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of severe combined immunodeficiency (PMID: 28039949, 29146883, 31696992). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 694006). 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 expected to disrupt LIG4 protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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