ClinVar Miner

Submissions for variant NM_000155.4(GALT):c.379A>G (p.Lys127Glu) (rs111033682)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000022098 SCV000798380 likely pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2018-03-09 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000723539 SCV000331278 uncertain significance not provided 2015-09-08 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000022098 SCV000695691 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2016-08-23 criteria provided, single submitter clinical testing Variant summary: The GALT c.379A>G (p.Lys127Glu) variant involves the alteration of a conserved nucleotide. 2/4 in silico tools predict a damaging outcome for this variant. This variant is located in the HIT-like domain (InterPro). Predicted structural consequences of this variant is misfolding of the protein (Facchiano_2010, McCorvie_2016). This variant was absent in 121412 control chromosomes. This variant is widely reported as pathogenic variant causing galactosemia with consistent patient and functional data. In addition, multiple reputable databases classified this variant as pathogenic. Taken together, this variant is classified as Pathogenic.
Invitae RCV000022098 SCV000830435 likely pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2018-05-03 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamic acid at codon 127 of the GALT protein (p.Lys127Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with galactosemia but no second allele was reported (PMID: 15841485, 15633893) and it has been reported in combination with another GALT variant in individuals who are affected with this condition including one with the Duarte allele and one where the variant is observed on the opposite chromosome (in trans) from a pathogenic variant (http://www.arup.utah.edu/database/GALT/GALT_display.php, PMID: 11397328, 22870861, Invitae). This latter finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 25167). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Research and Development, ARUP Laboratories RCV000022098 SCV000042774 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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