ClinVar Miner

Submissions for variant NM_206937.2(LIG4):c.1913T>C (p.Ile638Thr)

gnomAD frequency: 0.00009  dbSNP: rs372158210
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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 RCV001929257 SCV002198407 uncertain significance DNA ligase IV deficiency 2024-10-07 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 638 of the LIG4 protein (p.Ile638Thr). This variant is present in population databases (rs372158210, gnomAD 0.005%). 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: 1426152). 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.
Ambry Genetics RCV004044303 SCV004899206 uncertain significance Inborn genetic diseases 2021-08-12 criteria provided, single submitter clinical testing The c.1913T>C (p.I638T) alteration is located in exon 2 (coding exon 1) of the LIG4 gene. This alteration results from a T to C substitution at nucleotide position 1913, causing the isoleucine (I) at amino acid position 638 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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