ClinVar Miner

Submissions for variant NM_000155.4(GALT):c.855G>T (p.Lys285Asn) (rs111033773)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 11
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000003805 SCV000052475 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2011-08-18 criteria provided, single submitter curation Converted during submission to Pathogenic.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000224446 SCV000110077 pathogenic not provided 2018-06-12 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000224446 SCV000281425 pathogenic not provided 2015-09-14 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000003805 SCV000603795 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2018-11-05 criteria provided, single submitter clinical testing The GALT c.855G>T; p.Lys285Asn variant (rs111033773) is reported in multiple individuals diagnosed with classic galactosemia when found in trans with another pathogenic variant (Chhay 2008, Viggiano 2015). Functional characterization of the variant protein in red blood cells and yeast cells indicates severe reduction in GALT activity (Chhay 2008, Coelho 2014, Viggiano 2015). This variant is reported as pathogenic in ClinVar (Variation ID: 3621). It is found in the general population with an overall allele frequency of 0.01% (36/282874 alleles) in the Genome Aggregation Database. The lysine at codon 285 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Based on available information, the variant is considered to be pathogenic. REFERENCES Chhay J et al. A yeast model reveals biochemical severity associated with each of three variant alleles of galactose-1P uridylyltransferase segregating in a single family. J Inherit Metab Dis. 2008; 31(1):97-107. Coelho A et al. Functional and structural impact of the most prevalent missense mutations in classic galactosemia. Mol Genet Genomic Med. 2014; 2(6):484-96. Viggiano E et al. Clinical and molecular spectra in galactosemic patients from neonatal screening in northeastern Italy: structural and functional characterization of new variations in the galactose-1-phosphate uridyltransferase (GALT) gene. Gene. 2015; 559(2):112-8.
Invitae RCV000003805 SCV000813007 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2018-10-16 criteria provided, single submitter clinical testing This sequence change replaces lysine with asparagine at codon 285 of the GALT protein (p.Lys285Asn). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is present in population databases (rs111033773, ExAC 0.03%). This variant has been observed in individuals with low GALT enzyme activity, findings that are highly specific for galactose-1-phosphate uridylyltransferase deficiency (PMID: 18210213, 25592817, 16540753, Invitae). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in individuals affected with galactose-1-phosphate uridylyltransferase deficiency (PMID: 25592817, 16540753, Invitae). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 3621). Experimental studies have shown that this missense change results in a GALT protein with null enzymatic activity (PMID: 18210213, 11152465, 25614870). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000003805 SCV000894465 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2018-10-31 criteria provided, single submitter clinical testing
Baylor Genetics RCV000003805 SCV001163247 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase criteria provided, single submitter clinical testing
OMIM RCV000003805 SCV000023970 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 1997-01-01 no assertion criteria provided literature only
Research and Development, ARUP Laboratories RCV000003805 SCV000042903 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2012-12-04 no assertion criteria provided clinical testing Converted during submission to Pathogenic.
GeneReviews RCV000003805 SCV000147999 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2014-04-03 no assertion criteria provided literature only
Counsyl RCV000003805 SCV000678171 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2015-06-06 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.