ClinVar Miner

Submissions for variant NM_206937.2(LIG4):c.1847A>G (p.Tyr616Cys)

gnomAD frequency: 0.00005  dbSNP: rs778875030
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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 RCV001211230 SCV001382757 uncertain significance DNA ligase IV deficiency 2022-08-16 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 616 of the LIG4 protein (p.Tyr616Cys). This variant is present in population databases (rs778875030, 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: 941446). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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 RCV004033814 SCV004899204 uncertain significance Inborn genetic diseases 2024-01-23 criteria provided, single submitter clinical testing The c.1847A>G (p.Y616C) alteration is located in exon 2 (coding exon 1) of the LIG4 gene. This alteration results from a A to G substitution at nucleotide position 1847, causing the tyrosine (Y) at amino acid position 616 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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