Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| EGL Genetic Diagnostics, |
RCV000723398 | SCV000230859 | pathogenic | not provided | 2014-05-27 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000022114 | SCV000631392 | pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2017-06-14 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with glutamine at codon 148 of the GALT protein (p.Arg148Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs111033694, ExAC 0.009%). This variant has been reported as homozygous or in combination with other GALT variants in individuals affected with galactosemia (PMID: 7887416, 19375122, 15841485, 22944367). Experimental studies have shown that this missense change drastically reduces GALT enzymatic activity (PMID: 25614870). A different missense substitution at this codon (p.Arg148Trp) has been determined to be pathogenic (PMID: 7887416, 1373122, 15841485, 22944367, 25268296). This suggests that the arginine residue is critical for GALT protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic. |
| Counsyl | RCV000022114 | SCV000789695 | likely pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2017-02-10 | criteria provided, single submitter | clinical testing | |
| Integrated Genetics/Laboratory Corporation of America | RCV000022114 | SCV000917420 | pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2018-02-12 | criteria provided, single submitter | clinical testing | Variant summary: GALT c.443G>A (p.Arg148Gln) results in a conservative amino acid change located in the N-terminal of the Galactose-1-phosphate uridyl transferase, of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 246264 control chromosomes in gnomAD. This frequency is not significantly higher than expected for a pathogenic variant in GALT causing Galactosemia (2.8e-05 vs 2.90E-03), allowing no conclusion about variant significance. The variant, c.443G>A, has been reported in the literature in multiple individuals affected with Galactosemia (Elsas_1995, Bosch_2005, Gort_2009, Boutron_2012). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as "pathogenic." Based on the evidence outlined above, the variant was classified as pathogenic. |
| Baylor Genetics | RCV000022114 | SCV001163238 | pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | criteria provided, single submitter | clinical testing | ||
| Research and Development, |
RCV000022114 | SCV000042792 | pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2012-12-04 | no assertion criteria provided | clinical testing | Converted during submission to Pathogenic. |