ClinVar Miner

Submissions for variant NM_206937.2(LIG4):c.1337G>C (p.Gly446Ala)

gnomAD frequency: 0.00001  dbSNP: rs199934893
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000641092 SCV000762712 uncertain significance DNA ligase IV deficiency 2024-10-21 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 446 of the LIG4 protein (p.Gly446Ala). This variant is present in population databases (rs199934893, gnomAD 0.006%). 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: 533824). 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.
Breakthrough Genomics, Breakthrough Genomics RCV004692003 SCV005192215 uncertain significance not provided criteria provided, single submitter not provided

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