Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000022102 | SCV000800661 | uncertain significance | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2018-02-22 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV000022102 | SCV001158685 | likely pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2019-04-17 | criteria provided, single submitter | clinical testing | The GALT c.394C>T; p.His132Tyr variant (rs367543256) is reported in the in individuals affected with galactosemia (Elsas 1998, Powell 2009). Functional analyses demonstrate reduced enzyme activity when in the compound heterozygous state with the Duarte allele (Powell 2009). This variant is reported in ClinVar (Variation ID: 37357), and is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. Additionally, another variant at this codon (c.396C>A; p.His132Gln) has been reported in individuals with galactosemia and is considered pathogenic (Narravula 2017, Tang 2012). The histidine at codon 132 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. 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. Powell KK et al. Long-term speech and language developmental issues among children with Duarte galactosemia. Genet Med. 2009 Dec;11(12):874-9. Narravula A Variants of uncertain significance in newborn screening disorders: implications for large-scale genomic sequencing. Genet Med. 2017 Jan;19(1):77-82. Tang M et al. Correlation assessment among clinical phenotypes, expression analysis and molecular modeling of 14 novel variations in the human galactose-1-phosphate uridylyltransferase gene. Hum Mutat. 2012 Jul;33(7):1107-15. |
| Invitae | RCV000022102 | SCV003441335 | likely pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2022-06-13 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the p.His132 amino acid residue in GALT. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22461411, 22944367, 28649529; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GALT protein function. ClinVar contains an entry for this variant (Variation ID: 37357). This missense change has been observed in individual(s) with galactosemia (PMID: 11261429, 19904210, 27176039). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 132 of the GALT protein (p.His132Tyr). |
| Revvity Omics, |
RCV000022102 | SCV003834137 | likely pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2022-06-24 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV001831616 | SCV002085198 | likely pathogenic | Galactosemia | 2021-09-03 | no assertion criteria provided | clinical testing |