Submissions for variant NM_000352.6(ABCC8):c.1347_1348del (p.Ile450fs)

dbSNP: rs1554933565

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000674705	SCV000800091	likely pathogenic	Hyperinsulinemic hypoglycemia, familial, 1	2018-05-22	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV001816682	SCV002067529	pathogenic	not provided	2020-08-07	criteria provided, single submitter	clinical testing	This sequence change is a two base pair deletion in exon 9, c.1347_1348del. This sequence change results in an amino acid frameshift and creates a premature stop codon 43 amino acids downstream of the change, p.Ile450Serfs*44. This sequence change is predicted to result in an abnormal transcript, which may be degraded, or may lead to the production of a truncated ABCC8 protein with potentially abnormal function. This sequence change is absent from the large population databases such as ExAC and gnomAD. This sequence change has previously been described in a Diazoxide-responsive patient with CHI (PMID: 16429405).
Labcorp Genetics (formerly Invitae), Labcorp	RCV001816682	SCV002108012	pathogenic	not provided	2023-07-07	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ile450Serfs*44) 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 individual(s) with ABCC8-related conditions (PMID: 16429405). ClinVar contains an entry for this variant (Variation ID: 558438). For these reasons, this variant has been classified as Pathogenic.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002253561	SCV002522427	uncertain risk allele	Maturity onset diabetes mellitus in young	2024-05-27	criteria provided, single submitter	research	This variant is found to be a potent moderate impact variant with a sufficient scientific evidence to support gene-disease correlation. However, since this is not a high impact variant and has no variant evidence, this variant is reclassified as Uncertain Risk Allele
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV004556815	SCV002522428	uncertain risk allele	Neonatal diabetes mellitus	2024-05-27	criteria provided, single submitter	research	This variant is found to be a potent moderate impact, variant with a sufficient scientific evidence of gene-disease correlation. However, since this is not a high impact variant and no variant evidence, this variant is reclassified as Uncertain risk allele.