ClinVar Miner

Submissions for variant NM_000155.4(GALT):c.584T>C (p.Leu195Pro) (rs111033728)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000022158 SCV000052469 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2011-08-18 criteria provided, single submitter curation Converted during submission to Pathogenic.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000224416 SCV000110068 pathogenic not provided 2015-09-18 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000224416 SCV000280877 pathogenic not provided 2015-09-14 criteria provided, single submitter clinical testing
Invitae RCV000022158 SCV000818252 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2020-10-20 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 195 of the GALT protein (p.Leu195Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. This variant is present in population databases (rs111033728, ExAC 0.01%). This variant has been reported in several individuals affected with galactosemia, in many cases in combination with other known pathogenic variants in the GALT gene (PMID: 8598637, 10649501, 1373122, 19375122, 22944367). ClinVar contains an entry for this variant (Variation ID: 25222). Experimental studies have shown that this missense change reduces GALT enzymatic activity in vitro (PMID: 1373122). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000022158 SCV000893810 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2018-10-31 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000022158 SCV001160717 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2018-10-26 criteria provided, single submitter clinical testing The GALT c.584T>C; p.Leu195Pro variant (rs111033728), is reported in the literature in the compound heterozygous state with known pathogenic GALT variants in multiple individuals affected with mild to severe galactosemia (Boutron 2012, Kozak 2000, Reichardt 1992). This variant is reported as pathogenic by multiple laboratories in ClinVar (Variation ID: 25222), and is found in the non-Finnish European population with an allele frequency of 0.015% (17/113,764 alleles) in the Genome Aggregation Database. The leucine at codon 195 is moderately conserved, and computational analyses (SIFT: damaging, PolyPhen-2: benign) predict conflicting effects of this variant on protein structure/function. However, functional analyses of the variant protein show reduced GALT enzymatic activity in vitro (Reichardt 1992). Based on available information, the p.Leu195Pro variant is considered to be pathogenic. References: Boutron A et al. Mutation spectrum in the French cohort of galactosemic patients and structural simulation of 27 novel missense variations. Mol Genet Metab. 2012 Nov;107(3):438-47. Kozak L et al. Mutation analysis of the GALT gene in Czech and Slovak galactosemia populations: identification of six novel mutations, including a stop codon mutation (X380R). Hum Mutat. 2000 Feb;15(2):206. Reichardt JK et al. Characterization of two missense mutations in human galactose-1-phosphate uridyltransferase: different molecular mechanisms for galactosemia. Genomics. 1992 Mar;12(3):596-600.
Baylor Genetics RCV000022158 SCV001163240 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase criteria provided, single submitter clinical testing
Myriad Women's Health, Inc. RCV000022158 SCV001194049 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2019-12-09 criteria provided, single submitter clinical testing NM_000155.3(GALT):c.584T>C(L195P) is classified as pathogenic in the context of galactosemia. Sources cited for classification include the following: PMID 19375122, 1373122, 8598637, 10649501, 10960497, 15841485 and 11397328. Classification of NM_000155.3(GALT):c.584T>C(L195P) is based on the following criteria: This is a well-established pathogenic variant in the literature that 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.‚Äã
CeGaT Praxis fuer Humangenetik Tuebingen RCV000224416 SCV001246076 pathogenic not provided 2019-07-01 criteria provided, single submitter clinical testing
GeneDx RCV000224416 SCV001769942 pathogenic not provided 2020-11-25 criteria provided, single submitter clinical testing A common variant that has been estimated to represent approximately 2% of GALT mutant alleles in the US (Elsas et al., 1998); Published functional studies demonstrate a damaging effect (Reichardt et al. 1992); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 31589614, 31954591, 31194252, 22944367, 8598637, 27415407, 1373122, 17041746, 10649501, 20008339, 22975760, 11261429, 27604308)
Research and Development, ARUP Laboratories RCV000022158 SCV000042839 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2012-12-04 no assertion criteria provided clinical testing Converted during submission to Pathogenic.
GeneReviews RCV000022158 SCV000147996 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2021-03-09 no assertion criteria provided literature only Severe classic pathogenic variant

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