ClinVar Miner

Submissions for variant NM_000155.4(GALT):c.1018G>A (p.Glu340Lys)

gnomAD frequency: 0.00001  dbSNP: rs111033806
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000022263 SCV001377663 uncertain significance Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2022-10-21 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 340 of the GALT protein (p.Glu340Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with GALT-related conditions (PMID: 10649501, 20213376, 22944367, 28065439). ClinVar contains an entry for this variant (Variation ID: 25317). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GALT protein function. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001582494 SCV001821392 uncertain significance not specified 2021-08-26 criteria provided, single submitter clinical testing Variant summary: GALT c.1018G>A (p.Glu340Lys) results in a conservative amino acid change located in the Galactose-1-phosphate uridyl transferase, C-terminal domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251462 control chromosomes. c.1018G>A has been reported in the literature in individuals affected with Galactosemia in the homozygous and compound heterozygous state with the Duarte allele in cis (Kozak_2000, Milankovics_2010), the compound heterozygous without reporting the of presence of Duarte allele (Siripunthana_2013) and in the heterozygous state without a reported second allele and unknown Duarte allele status (Welling_2017). The penetrance of the variant in isolation is unknown. Additionally, to our knowledge, no experimental studies have been performed on this variant in isolation. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Baylor Genetics RCV000022263 SCV004198538 likely pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2023-06-12 criteria provided, single submitter clinical testing
Natera, Inc. RCV001826503 SCV002085255 uncertain significance Galactosemia 2021-08-10 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.