ClinVar Miner

Submissions for variant NM_000154.2(GALK1):c.202C>T (p.Arg68Cys)

gnomAD frequency: 0.00001  dbSNP: rs1365349586
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000669092 SCV000793796 uncertain significance Deficiency of galactokinase 2017-08-30 criteria provided, single submitter clinical testing
Invitae RCV000669092 SCV003442516 uncertain significance Deficiency of galactokinase 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 68 of the GALK1 protein (p.Arg68Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with galactokinase deficiency galactosemia (PMID: 11139256). ClinVar contains an entry for this variant (Variation ID: 553609). 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: "Probably Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects GALK1 function (PMID: 12694189). 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 RCV003230567 SCV003928811 uncertain significance not specified 2023-04-06 criteria provided, single submitter clinical testing Variant summary: GALK1 c.202C>T (p.Arg68Cys) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 216368 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.202C>T has been reported in the literature in at least one compound heterozygous individual affected with Deficiency Of Galactokinase (Hunter_2001). The report does not provide unequivocal conclusions about association of the variant with Deficiency Of Galactokinase. At least one invitro study reports experimental evidence evaluating an impact on protein function and this variant results in less active than the wild-type enzyme (Timson_2003). Two ClinVar submitters (evaluation after 2014) cite this variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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