ClinVar Miner

Submissions for variant NM_001099922.3(ALG13):c.1643T>C (p.Val548Ala)

gnomAD frequency: 0.00001  dbSNP: rs1238751751
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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 RCV001066153 SCV001231153 uncertain significance Developmental and epileptic encephalopathy, 36 2022-09-23 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 548 of the ALG13 protein (p.Val548Ala). This variant is present in population databases (no rsID available, gnomAD 0.008%). This missense change has been observed in individual(s) with clinical features of ALG13-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 859933). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003396710 SCV004122736 uncertain significance not specified 2023-10-11 criteria provided, single submitter clinical testing Variant summary: ALG13 c.1643T>C (p.Val548Ala) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.1e-05 in 178869 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1643T>C in individuals affected with Epileptic Encephalopathy, Early Infantile, 36 and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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