Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000022185 | SCV000826865 | pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2023-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 231 of the GALT protein (p.Arg231His). This variant is present in population databases (rs111033754, gnomAD no frequency). This missense change has been observed in individual(s) with Galactose-1-phosphate uridylyltransferase deficiency (PMID: 7550229, 22944367, 27176039). ClinVar contains an entry for this variant (Variation ID: 25247). 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. Experimental studies have shown that this missense change affects GALT function (PMID: 7550229, 11152465, 25614870). This variant disrupts the p.Arg231 amino acid residue in GALT. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 14518827, 22944367, 25614870, 25814382). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000022185 | SCV001983411 | pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2021-09-23 | criteria provided, single submitter | clinical testing | Variant summary: GALT c.692G>A (p.Arg231His) results in a non-conservative amino acid change located in the Galactose-1-phosphate uridyl transferase, C-terminal domain (IPR005850) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250550 control chromosomes (gnomAD). c.692G>A has been reported in the literature in multiple individuals affected with Galactosemia, including one homozygote (Ashino_1995, Ozgul_2013). These data indicate that the variant is very likely to be associated with disease. Functional studies report experimental evidence evaluating an impact on protein function and this variant results in absent GALT enzyme activity (Ashino_1995, Hirokawa_1999, Riehman_2001, Coelho_2014). One ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Myriad Genetics, |
RCV000022185 | SCV002060145 | likely pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2021-11-03 | criteria provided, single submitter | clinical testing | NM_000155.3(GALT):c.692G>A(R231H) is a missense variant classified as likely pathogenic in the context of galactosemia. R231H has been observed in cases with relevant disease (PMID: 7550229, 22944367, 23924834, 27176039). Functional assessments of this variant are available in the literature (PMID: 11152465, 25614870). R231H has been observed in population frequency databases (gnomAD: OTH 0.02%). In summary, NM_000155.3(GALT):c.692G>A(R231H) is a missense variant that has been observed more frequently in cases with the relevant disease than in healthy populations. |
Mayo Clinic Laboratories, |
RCV002254268 | SCV002525790 | pathogenic | not provided | 2021-08-13 | criteria provided, single submitter | clinical testing | PP3, PP4, PM2, PM5, PS3, PS4 |
Baylor Genetics | RCV000022185 | SCV004198501 | pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2023-10-17 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001826498 | SCV002085230 | pathogenic | Galactosemia | 2017-08-29 | no assertion criteria provided | clinical testing |