ClinVar Miner

Submissions for variant NM_000352.6(ABCC8):c.3509del (p.Leu1170fs)

dbSNP: rs587783169
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000144992 SCV000192028 pathogenic Hyperinsulinemic hypoglycemia, familial, 1 2014-05-12 criteria provided, single submitter clinical testing
Counsyl RCV000144992 SCV000798188 pathogenic Hyperinsulinemic hypoglycemia, familial, 1 2018-03-05 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001070454 SCV001235686 pathogenic not provided 2025-01-01 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu1170Argfs*38) in the ABCC8 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCC8 are known to be pathogenic (PMID: 20685672, 23345197). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with autosomal recessive congenital hyperinsulinism (PMID: 23275527, 24686051). This variant is also known as c.3512delT (p.Leu1171Argfs*38). ClinVar contains an entry for this variant (Variation ID: 157696). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001251322 SCV001426874 pathogenic Familial hyperinsulinism 2020-07-23 criteria provided, single submitter clinical testing Variant summary: ABCC8 c.3509delT (p.Leu1170ArgfsX38) 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. The variant was absent in 251406 control chromosomes (gnomAD). c.3509delT has been reported in the literature in multiple individuals affected with Congenital Hyperinsulinism (Calton_2012, Snider_2013, Kapoor_2013, Demirbilek_2014). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics RCV003467205 SCV004192609 pathogenic Type 2 diabetes mellitus 2023-06-20 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005049430 SCV005681097 pathogenic Diabetes mellitus, transient neonatal, 2; Hyperinsulinemic hypoglycemia, familial, 1; Leucine-induced hypoglycemia; Type 2 diabetes mellitus; Diabetes mellitus, permanent neonatal 3 2024-04-08 criteria provided, single submitter clinical testing
Natera, Inc. RCV001277189 SCV001464087 pathogenic Hereditary hyperinsulinism 2020-09-16 no assertion criteria provided clinical testing

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