ClinVar Miner

Submissions for variant NM_000352.6(ABCC8):c.4612C>T (p.Arg1538Ter)

dbSNP: rs1411638309
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000672393 SCV000797492 likely pathogenic Hyperinsulinemic hypoglycemia, familial, 1 2018-01-29 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001379884 SCV001577769 pathogenic not provided 2022-09-06 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the ABCC8 protein in which other variant(s) (p.Leu1543Pro) have been determined to be pathogenic (PMID: 11867634, 15562009, 23275527). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 556392). This variant has not been reported in the literature in individuals affected with ABCC8-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg1538*) in the ABCC8 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 44 amino acid(s) of the ABCC8 protein.
GeneDx RCV001379884 SCV003924894 likely pathogenic not provided 2022-11-11 criteria provided, single submitter clinical testing Identified as heterozygous in a patient with hyperinsulinism in published literature (De Franco et al., 2020); Nonsense variant predicted to result in protein truncation, as the last 44 amino acids are lost, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32027066)
Fulgent Genetics, Fulgent Genetics RCV005046897 SCV005676648 likely pathogenic Diabetes mellitus, transient neonatal, 2; Hyperinsulinemic hypoglycemia, familial, 1; Leucine-induced hypoglycemia; Type 2 diabetes mellitus; Diabetes mellitus, permanent neonatal 3 2024-04-26 criteria provided, single submitter clinical testing

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