Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000404302 | SCV000339869 | likely pathogenic | not provided | 2016-02-22 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001382082 | SCV001580712 | pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2023-10-11 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with serine, which is neutral and polar, at codon 251 of the GALT protein (p.Tyr251Ser). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This missense change has been observed in individual(s) with galactosemia (PMID: 11397328, 11754113; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 286433). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the p.Tyr251 amino acid residue in GALT. Other variant(s) that disrupt this residue have been observed in individuals with GALT-related conditions (PMID: 10384398), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
| ARUP Laboratories, |
RCV001382082 | SCV002048992 | likely pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2021-08-06 | criteria provided, single submitter | clinical testing | The GALT c.752_753delinsCT; p.Tyr251Ser variant (rs886043390), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 286433). However, other variants at this codon, including one resulting in the same amino acid change (c.752A>C; p.Tyr251Ser; c.752A>G; p.Tyr251Cys), have been reported in individuals with galactosemia (Elsas 1998, Robertson 2000, Shin 1999, Tyfield 1999, Yang 2002). The c.752_753delinsCT; p.Tyr251Ser variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. The tyrosine at codon 251 is weakly conserved, but computational analyses predict that this variant is deleterious (REVEL: 0.975). Based on available information, this variant is considered to be likely pathogenic. References: Elsas LJ 2nd and Lai K. The molecular biology of galactosemia. Genet Med. 1998 Nov-Dec;1(1):40-8. PMID: 11261429. Robertson A et al. Outcomes analysis of verbal dyspraxia in classic galactosemia. Genet Med. 2000 Mar-Apr;2(2):142-8. PMID: 11397328. Shin YS et al. Molecular and biochemical basis for variants and deficiency forms of galactose-1-phosphate uridyltransferase. J Inherit Metab Dis. 1999 May;22(3):327-9. PMID: 10384398. Tyfield L et al. Classical galactosemia and mutations at the galactose-1-phosphate uridyl transferase (GALT) gene. Hum Mutat. 1999;13(6):417-30. PMID: 10408771. Yang YP et al. Molecular analysis in newborns from Texas affected with galactosemia. Hum Mutat. 2002 Jan;19(1):82-3. PMID: 11754113. |