Submissions for variant NM_000155.3(GALT):c.790_792invCTA (p.Leu264Ter)

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics	RCV000723483	SCV000110074	pathogenic	not provided	2013-04-19	criteria provided, single submitter	clinical testing
Invitae	RCV000555777	SCV000631391	pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2017-06-27	criteria provided, single submitter	clinical testing	This sequence change deletes 3 nucleotide and inserts 3 nucleotides in exon 8 of the GALT mRNA (c.790_792invCTA), creating a premature translational stop signal (p.Leu264*) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in GALT are known to be pathogenic (PMID: 22944367). This particular variant has been reported in the literature in several individuals affected with galactosemia (PMID: 11754113, 11261429, Invitae). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000555777	SCV000695704	pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2020-12-19	criteria provided, single submitter	clinical testing	Variant summary: GALT c.790_792delinsTAG (p.Leu264X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 245500 control chromosomes. c.790_792delinsTAG has been reported in the literature in individuals affected with Galactosemia (example, Elsas_1998, Yang_2002, Demirbas_2019 and an external laboratory database). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. 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 pathogenic citing overlapping evidence utilized in the context of this evaluation. Based on the evidence outlined above, the variant was classified as pathogenic.
GeneDx	RCV000723483	SCV001783165	pathogenic	not provided	2021-06-30	criteria provided, single submitter	clinical testing	Observed in apparent homozygous state in a patient with a confirmed diagnosis of classic galactosemia (Elsas et al., 1998); Not observed in large population cohorts (Lek et al., 2016); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 11261429, 30718057, 11754113, 10408771)
Research and Development, ARUP Laboratories	RCV000555777	SCV000055335	pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2012-12-04	no assertion criteria provided	clinical testing	Converted during submission to Pathogenic.