ClinVar Miner

Submissions for variant NM_000352.6(ABCC8):c.1290G>A (p.Trp430Ter)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV003322273 SCV004026565 likely pathogenic Hyperinsulinemic hypoglycemia, familial, 1 2023-08-16 criteria provided, single submitter curation The p.Trp430Ter variant in ABCC8 has been reported in 1 individual with hyperinsulinemic hypoglycemia (PMID: 36239000), and has been identified in 0.003% (1/34592) of Latino/Admixed American chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs767500007). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This nonsense variant leads to a premature termination codon at position 430, which is predicted to lead to a truncated or absent protein. Loss of function of the ABCC8 gene is an established disease mechanism in autosomal recessive hyperinsulinemic hypoglycemia. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal recessive hyperinsulinemic hypoglycemia. ACMG/AMP Criteria applied: PVS1, PM2 (Richards 2015).
GeneDx RCV004763649 SCV005370548 pathogenic not provided 2023-06-28 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23275527, 21422196, 36239000)

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