ClinVar Miner

Submissions for variant NM_001164277.1(SLC37A4):c.359dup (p.Cys121fs) (rs1182102272)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000781849 SCV000920220 likely pathogenic Glucose-6-phosphate transport defect 2018-02-19 criteria provided, single submitter clinical testing Variant summary: SLC37A4 c.359dupC (p.Cys121MetfsX10) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. c.742C>T (p.Gln248X), c.1042_1043delCT (p.Leu348fsX53)). The variant allele was found at a frequency of 1.6e-05 in 254374 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in SLC37A4 causing Glycogen Storage Disease Type Ib (1.6e-05 vs 1.20E-03), allowing no conclusion about variant significance. c.359dupC has been reported in the literature in individuals affected with Glycogen Storage Disease Type Ib (Janecke 2000, Santer 2000). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV000781849 SCV001202834 pathogenic Glucose-6-phosphate transport defect 2019-11-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Cys121Metfs*10) in the SLC37A4 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with glycogen storage disease (PMID: 10482962). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as 528_529insC in the literature. ClinVar contains an entry for this variant (Variation ID: 633417). Loss-of-function variants in SLC37A4 are known to be pathogenic (PMID: 9758626, 10940311). For these reasons, this variant has been classified as Pathogenic.

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