ClinVar Miner

Submissions for variant NM_000155.4(GALT):c.772C>T (p.Arg258Cys) (rs368166217)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000493672 SCV000885498 likely pathogenic not provided 2017-08-01 criteria provided, single submitter clinical testing
Counsyl RCV000078235 SCV000800530 uncertain significance Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2017-05-17 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000493672 SCV000110073 pathogenic not provided 2013-07-16 criteria provided, single submitter clinical testing
GeneDx RCV000493672 SCV000582974 likely pathogenic not provided 2016-03-15 criteria provided, single submitter clinical testing The R258C variant has been reported in a patient with elevated galatose-1-phosphate and liver enzymes during the newborn period (Shin et al., 1999). The R258C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (P257T/L/R, R259W/Q, R262P, R263Q) have been reported in the Human Gene Mutation Database in association with galactosemia (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, R258C was interpreted to be a likely pathogenic variant.
Invitae RCV000078235 SCV000931179 uncertain significance Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2018-11-19 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 258 of the GALT protein (p.Arg258Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs368166217, ExAC 0.007%). This variant has been observed in individuals affected with galactosemia and has been defined as mild variant (PMID: 10960497, 15633893). ClinVar contains an entry for this variant (Variation ID: 92522). 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: "Probably 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.

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