ClinVar Miner

Submissions for variant NM_000155.4(GALT):c.554C>T (p.Pro185Leu)

dbSNP: rs111033722
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000022149 SCV000800588 uncertain significance Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2017-11-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000022149 SCV001230883 uncertain significance Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2024-01-07 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 185 of the GALT protein (p.Pro185Leu). This variant is present in population databases (rs111033722, gnomAD 0.006%). This missense change has been observed in individual(s) with galactosemia (PMID: 23022339). ClinVar contains an entry for this variant (Variation ID: 25213). 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 with a positive predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001844015 SCV002103376 uncertain significance not specified 2024-06-11 criteria provided, single submitter clinical testing Variant summary: GALT c.554C>T (p.Pro185Leu) results in a non-conservative amino acid change located in the Galactose-1-phosphate uridyl transferase, N-terminal domain (IPR005849) 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 8e-06 in 251476 control chromosomes. c.554C>T has been reported in the literature in the compound heterozygous state with the c.[940A>G;-119_-116delGTCA] Duarte variant (D2) in at least 2 individuals affected with biochemically and clinically confirmed Galactosemia (example, Singh_2012). 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. The following publication has been ascertained in the context of this evaluation (PMID: 23022339). ClinVar contains an entry for this variant (Variation ID: 25213). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Natera, Inc. RCV001826495 SCV002085217 uncertain significance Galactosemia 2020-07-22 no assertion criteria provided clinical testing

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