ClinVar Miner

Submissions for variant NM_000352.6(ABCC8):c.35C>A (p.Ser12Ter)

dbSNP: rs1283621955
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001212753 SCV001384348 pathogenic not provided 2019-09-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser12*) in the ABCC8 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in ABCC8 are known to be pathogenic (PMID: 20685672, 23345197). This variant has been observed in an individual affected with hyperinsulinism (PMID: 23345197).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001779134 SCV002014918 pathogenic Familial hyperinsulinism 2021-10-15 criteria provided, single submitter clinical testing Variant summary: ABCC8 c.35C>A (p.Ser12X) 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 221046 control chromosomes. c.35C>A has been reported in the literature in individuals affected with paternally inherited, diazoxide resistant form of focal Congenital Hyperinsulinism (example, Kapoor_2013, Arya_2014, Craigie_2018) although an association in settings of autosomal recessive diffuse congenital hyperinsulinism cannot be excluded. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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