Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Integrated Genetics/Laboratory Corporation of America | RCV000022254 | SCV000919406 | likely pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2018-11-26 | criteria provided, single submitter | clinical testing | Variant summary: GALT c.983G>A (p.Arg328His) results in a non-conservative amino acid change located in the Galactose-1-phosphate uridyl transferase, C-terminal domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function, including one computational study that considers the Arg328 H-bond with Arg-51 essential for protein function (Facchiano_2009). The variant allele was found at a frequency of 4.1e-06 in 246246 control chromosomes (gnomAD). The variant, c.983G>A, has been reported in the literature in individuals affected with Galactosemia, including a homozygote (Ozgul_2013, Elsas_1998). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014, with one lab calling it pathogenic in 2012. A different variant affecting the same codon, c.982C>T (p.Arg328Cys), was classified as likely pathogenic internally, suggesting this codon could play an important role in protein function. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Research and Development, |
RCV000022254 | SCV000042938 | pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2012-12-04 | no assertion criteria provided | clinical testing | Converted during submission to Pathogenic. |