ClinVar Miner

Submissions for variant NM_000352.6(ABCC8):c.4324G>A (p.Glu1442Lys)

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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 RCV003322279 SCV004026590 uncertain significance Hyperinsulinemic hypoglycemia, familial, 1 2023-08-16 criteria provided, single submitter curation The p.Glu1442Lys variant in ABCC8 has been reported in 1 individual with hyperinsulinemic hypoglycemia (PMID: 34304300), and has been identified in 0.007% (2/26692) of South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs759663539). 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. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Glu1442Lys variant is uncertain. ACMG/AMP Criteria applied: PP3, PM2_supporting (Richards 2015).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004690400 SCV005185190 uncertain significance not specified 2024-05-20 criteria provided, single submitter clinical testing Variant summary: ABCC8 c.4324G>A (p.Glu1442Lys) results in a conservative amino acid change located in the ABC transporter-like, ATP-binding domain (IPR003439) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 9.3e-06 in 215940 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4324G>A has been reported in the literature in at least one individual affected with congenital hyperinsulinism (example: Panigraphy_2021). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 33046911, 34304300). ClinVar contains an entry for this variant (Variation ID: 2576218). Based on the evidence outlined above, the variant was classified as uncertain significance.

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