ClinVar Miner

Submissions for variant NM_000154.2(GALK1):c.856C>T (p.Arg286Trp)

gnomAD frequency: 0.00005  dbSNP: rs370987432
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000313550 SCV000406619 uncertain significance Deficiency of galactokinase 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV000313550 SCV003514552 uncertain significance Deficiency of galactokinase 2021-08-24 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 286 of the GALK1 protein (p.Arg286Trp). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs370987432, ExAC 0.008%). This variant has not been reported in the literature in individuals affected with GALK1-related conditions. ClinVar contains an entry for this variant (Variation ID: 325228). 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: "Deleterious"; PolyPhen-2: "Benign"; 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.
Ambry Genetics RCV003258765 SCV003977699 uncertain significance Inborn genetic diseases 2023-03-28 criteria provided, single submitter clinical testing The c.856C>T (p.R286W) alteration is located in exon 6 (coding exon 6) of the GALK1 gene. This alteration results from a C to T substitution at nucleotide position 856, causing the arginine (R) at amino acid position 286 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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