ClinVar Miner

Submissions for variant NM_000340.2(SLC2A2):c.593C>T (p.Thr198Met) (rs149460434)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000650225 SCV000772063 uncertain significance Fanconi-Bickel syndrome 2019-02-28 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 198 of the SLC2A2 protein (p.Thr198Met). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs149460434, ExAC 0.02%). This variant has not been reported in the literature in individuals with SLC2A2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Illumina Clinical Services Laboratory,Illumina RCV000650225 SCV001310305 uncertain significance Fanconi-Bickel syndrome 2017-06-26 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001355604 SCV001550535 uncertain significance not provided no assertion criteria provided clinical testing The SLC2A2 p.T198M variant was not identified in the literature but was identified in dbSNP (ID: rs149460434) and ClinVar (classified as uncertain significance by Invitae for Fanconi-Bickel syndrome). The variant was identified in control databases in 28 of 281768 chromosomes at a frequency of 0.00009937 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: South Asian in 7 of 30594 chromosomes (freq: 0.000229), European (non-Finnish) in 20 of 128482 chromosomes (freq: 0.000156) and Latino in 1 of 35248 chromosomes (freq: 0.000028), but was not observed in the African, Ashkenazi Jewish, East Asian, European (Finnish), or Other populations. The p.T198 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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