ClinVar Miner

Submissions for variant NM_000155.4(GALT):c.200G>A (p.Arg67His) (rs758430398)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000634556 SCV000755885 uncertain significance Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2018-01-08 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 67 of the GALT protein (p.Arg67His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in an individual with an absence of GALT enzyme activity, a finding that is highly specific for galactosemia (PMID: 22944367). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). A different missense substitution at this codon (p.Arg67Cys) has been determined to be pathogenic (PMID: 8598637, 22944367, 11152465). This suggests that the arginine residue is critical for GALT protein function and that other missense substitutions at this position may also be pathogenic. 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.
Counsyl RCV000634556 SCV000795523 uncertain significance Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2017-11-08 criteria provided, single submitter clinical testing

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