ClinVar Miner

Submissions for variant NM_000155.4(GALT):c.815G>A (p.Arg272His) (rs111033831)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics 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
Invitae RCV000022210 SCV000835336 likely pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2018-05-15 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 272 of the GALT protein (p.Arg272His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs111033831, ExAC 0.009%). This variant has been reported in individuals affected with galactosemia (PMID: 22944367). ClinVar contains an entry for this variant (Variation ID: 38277). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). A different missense variant at the same codon (p.Arg272Cys) has been reported in the literature in individuals affected with galactosemia (PMID: 20151200). 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.
Integrated Genetics/Laboratory Corporation of America 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.
Research and Development, ARUP Laboratories RCV000022210 SCV000042892 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2012-12-04 no assertion criteria provided clinical testing Converted during submission to Pathogenic.

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