ClinVar Miner

Submissions for variant NM_000155.4(GALT):c.199C>T (p.Arg67Cys) (rs111033658)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000723719 SCV000110053 pathogenic not provided 2013-07-30 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000022067 SCV000917422 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2018-05-07 criteria provided, single submitter clinical testing Variant summary: GALT c.199C>T (p.Arg67Cys) results in a non-conservative amino acid change located in the Galactose-1-phosphate uridyl transferase, N-terminal (IPR005849) domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 30924 control chromosomes (gnomAD). c.199C>T has been reported in the literature in individuals affected with Galactosemia (Sommer 1995, Boutron 2012). These data indicate that the variant may be associated with disease. Two publications reported experimental evidence evaluating an impact on protein function (Sommer 1995, Riehman 2001). The most pronounced variant effect resulted in <10% of normal activity. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000022067 SCV000631389 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2018-10-31 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 67 of the GALT protein (p.Arg67Cys). 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 variant has been reported in the homozygous and compound heterozygous state in individuals affected with galactosemia (PMID: 8598637, 22944367). ClinVar contains an entry for this variant (Variation ID: 25137). Experimental studies have shown that this missense change reduces the GALT enzymatic activity in vitro and is not able to functionally rescue yeasts cells null for GALT (PMID: 11152465). For these reasons, this variant has been classified as Pathogenic.
Research and Development, ARUP Laboratories RCV000022067 SCV000042742 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2012-12-04 no assertion criteria provided clinical testing Converted during submission to Pathogenic.

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