ClinVar Miner

Submissions for variant NM_206937.2(LIG4):c.1437G>T (p.Met479Ile)

gnomAD frequency: 0.00006  dbSNP: rs529839175
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001883345 SCV002140750 uncertain significance DNA ligase IV deficiency 2024-12-09 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 479 of the LIG4 protein (p.Met479Ile). This variant is present in population databases (rs529839175, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with LIG4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1375422). Invitae Evidence 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 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. 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.
Mayo Clinic Laboratories, Mayo Clinic RCV004793557 SCV005409643 uncertain significance not provided 2024-07-09 criteria provided, single submitter clinical testing BP4
Ambry Genetics RCV004988839 SCV005606791 uncertain significance Inborn genetic diseases 2024-10-16 criteria provided, single submitter clinical testing The c.1437G>T (p.M479I) alteration is located in exon 2 (coding exon 1) of the LIG4 gene. This alteration results from a G to T substitution at nucleotide position 1437, causing the methionine (M) at amino acid position 479 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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