Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Integrated Genetics/Laboratory Corporation of America | RCV000022167 | SCV000052471 | pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2011-08-18 | criteria provided, single submitter | curation | Converted during submission to Pathogenic. |
EGL Genetic Diagnostics, |
RCV000185918 | SCV000110069 | pathogenic | not provided | 2016-05-06 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000185918 | SCV000238871 | pathogenic | not provided | 2018-04-13 | criteria provided, single submitter | clinical testing | The Y209C variant is a common pathogenic variant in the Caucasian population and has been reported in several unrelated individuals with galactosemia (Elsas et al., 1998; Zekanowski et al., 1999; Malone et al., 2011; Sartippour et al., 2014). Functional analysis of Y209C found that it is associated with significantly reduced, but not absent GALT activity (Liu et al., 2012). The Y209C variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The Y209C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. In summary, we interpret Y209C to be a pathogenic variant. |
Center for Pediatric Genomic Medicine, |
RCV000185918 | SCV000281374 | pathogenic | not provided | 2015-09-14 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000022167 | SCV000952487 | pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2019-03-29 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with cysteine at codon 209 of the GALT protein (p.Tyr209Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs111033744, ExAC 0.006%). This variant has been observed in several individuals affected with galactosemia (PMID: 11397328, 16540753, 10399107). ClinVar contains an entry for this variant (Variation ID: 25231). Experimental studies have shown that this missense change reduces GALT enzymatic activity (PMID: 22743281). This variant disrupts the p.Tyr209 amino acid residue in GALT. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 10399107), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV000022167 | SCV001163243 | pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | criteria provided, single submitter | clinical testing | ||
Myriad Women's Health, |
RCV000022167 | SCV001193851 | likely pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2019-12-13 | criteria provided, single submitter | clinical testing | NM_000155.3(GALT):c.626A>G(Y209C) is classified as likely pathogenic in the context of galactosemia. Sources cited for classification include the following: PMID 12595586, 10960497, 22693313, 11261429, 10399107 and 22743281. Classification of NM_000155.3(GALT):c.626A>G(Y209C) is based on the following criteria: This variant has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening. |
Research and Development, |
RCV000022167 | SCV000042849 | pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2012-12-04 | no assertion criteria provided | clinical testing | Converted during submission to Pathogenic. |
Gene |
RCV000022167 | SCV000147998 | pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2014-04-03 | no assertion criteria provided | literature only |