ClinVar Miner

Submissions for variant NM_000155.4(GALT):c.617A>G (p.Gln206Arg) (rs1587239309)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000805776 SCV000945744 uncertain significance Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2019-03-28 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 206 of the GALT protein (p.Gln206Arg). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with galactosemia (PMID: 22743281). 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: "Possibly 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.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000805776 SCV001157990 likely pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2018-11-06 criteria provided, single submitter clinical testing The GALT c.617A>G; p.Gln206Arg variant is reported in the literature in the homozygous state in an individual with classic galactosemia (Liu 2012). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The glutamine at codon 206 is moderately conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Consistent with these predictions, an in vitro GALT assay suggested the p.Gln206Arg variant exhibits negligible activity compared to wildtype protein (Spencer 2013). Based on available information, this variant is considered to be likely pathogenic. References: Liu Y et al. N- and O-linked glycosylation of total plasma glycoproteins in galactosemia. Mol Genet Metab. 2012 Aug;106(4):442-54. Spencer JB et al. Modifiers of ovarian function in girls and women with classic galactosemia. J Clin Endocrinol Metab. 2013 Jul;98(7):E1257-65.

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