ClinVar Miner

Submissions for variant NM_000155.4(GALT):c.425T>A (p.Met142Lys) (rs111033695)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000003793 SCV000790356 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2017-03-16 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000185916 SCV000110060 pathogenic not provided 2013-11-14 criteria provided, single submitter clinical testing
GeneDx RCV000185916 SCV000238869 pathogenic not provided 2018-12-28 criteria provided, single submitter clinical testing The M142K missense mutation in the GALT gene has been reported previously in association with classic galactosemia (Reichardt, J. and Woo, S., 1991). Expression of the M142K mutation in COS cells was associated with a severe reduction in galactose-1-phosphate uridyltransferase (GALT) enzyme activity compared to wild type (Reichardt, J. and Woo, S., 1991). Furthermore, other missense mutations at M142 (M142T, M142V) have been reported in association with classic galactosemia. The variant is found in GALT panel(s).
Invitae RCV000003793 SCV000755882 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2017-09-18 criteria provided, single submitter clinical testing This sequence change replaces methionine with lysine at codon 142 of the GALT protein (p.Met142Lys). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and lysine. This variant is present in population databases (rs111033695, ExAC 0.007%). This variant has been reported as homozygous or in combination with another GALT variant in several individuals affected with galactosemia (PMID: 10384398, 10960497, 17041746, 2011574, 20213376, 22944367, 23924834). ClinVar contains an entry for this variant (Variation ID: 3609). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000003793 SCV000023958 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 1991-04-01 no assertion criteria provided literature only
Research and Development, ARUP Laboratories RCV000003793 SCV000042787 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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