ClinVar Miner

Submissions for variant NM_206937.2(LIG4):c.1193G>A (p.Gly398Asp)

gnomAD frequency: 0.00001  dbSNP: rs538646268
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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 RCV000802702 SCV000942544 uncertain significance DNA ligase IV deficiency 2022-05-29 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 398 of the LIG4 protein (p.Gly398Asp). This variant is present in population databases (rs538646268, gnomAD 0.1%). 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: 648059). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
GeneDx RCV001766664 SCV002000792 uncertain significance not provided 2020-02-25 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002537149 SCV003756178 uncertain significance Inborn genetic diseases 2021-08-12 criteria provided, single submitter clinical testing The c.1193G>A (p.G398D) alteration is located in exon 2 (coding exon 1) of the LIG4 gene. This alteration results from a G to A substitution at nucleotide position 1193, causing the glycine (G) at amino acid position 398 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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