ClinVar Miner

Submissions for variant NM_001164277.1(SLC37A4):c.742C>T (p.Gln248Ter) (rs781784543)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169082 SCV000220256 likely pathogenic Glucose-6-phosphate transport defect 2014-04-21 criteria provided, single submitter literature only
GeneDx RCV000300702 SCV000330663 pathogenic not provided 2018-07-20 criteria provided, single submitter clinical testing The Q248X pathogenic variant in the SLC37A4 gene has been reported previously in association with glycogen storage disease type 1b when present in the homozygous state or when in trans with another pathogenic variant (Veiga-da-Cunha et al., 1998; Melis et al., 2005; Jun et al., 2014). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Q248X variant was not observed in approximately 6,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret Q248X as a pathogenic variant.
Integrated Genetics/Laboratory Corporation of America RCV000169082 SCV000697757 pathogenic Glucose-6-phosphate transport defect 2016-07-28 criteria provided, single submitter clinical testing Variant summary: The SLC37A4 c.742C>T (p.Gln248X) variant results in a premature termination codon, predicted to cause a truncated or absent SLC37A4 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. This variant was found in 2/118148 control chromosomes at a frequency of 0.0000169, which does not exceed the estimated maximal expected allele frequency of a pathogenic SLC37A4 variant (0.0012247). This variant has been reported in multiple GSD type 1b patients both homozygously and heterozygously. In addition, one clinical diagnostic laboratory classified this variant as likely pathogenic, without evidence to independently evaluate. Taken together, this variant is classified as pathogenic.
Invitae RCV000169082 SCV000949803 pathogenic Glucose-6-phosphate transport defect 2018-10-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln248*) in the SLC37A4 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs781784543, ExAC 0.009%). This variant has been observed as a homozygous in individuals affected with glycogen storage disease type Ib (PMID: 9758626, 10026167, 18437526). ClinVar contains an entry for this variant (Variation ID: 188762). 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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