Submissions for variant NM_000155.4(GALT):c.815G>A (p.Arg272His)

dbSNP: rs111033831

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000302160	SCV000336687	uncertain significance	not provided	2015-10-26	criteria provided, single submitter	clinical testing
Counsyl	RCV000022210	SCV000800754	likely pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2017-04-12	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000022210	SCV000835336	pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2025-01-14	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 272 of the GALT protein (p.Arg272His). This variant is present in population databases (rs111033831, gnomAD 0.003%). This missense change has been observed in individual(s) with galactosemia (PMID: 22944367; internal data). ClinVar contains an entry for this variant (Variation ID: 38277). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt GALT protein function with a positive predictive value of 95%. This variant disrupts the p.Arg272 amino acid residue in GALT. Other variant(s) that disrupt this residue have been observed in individuals with GALT-related conditions (PMID: 20151200), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000780280	SCV000917418	uncertain significance	not specified	2017-10-06	criteria provided, single submitter	clinical testing	Variant summary: The GALT c.815G>A (p.Arg272His) variant involves the alteration of a conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 2/245620 control chromosomes (gnomAD) at a frequency of 0.0000081, which does not exceed the estimated maximal expected allele frequency of a pathogenic GALT variant (0.0028868). This variant has been reported in three patients in compound heterozygous state with another pathogenic mutation (Boutron_2012). Another missense change at the same residue Arg272Gly has also been reported in a patient with galactesemia and is classified as pathogenic by a database in ClinVar. Taken together, this variant is classified as VUS - possibly pathogenic.
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV000022210	SCV002570109	likely pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase		criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000022210	SCV004198494	pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2023-12-20	criteria provided, single submitter	clinical testing