Submissions for variant NC_000011.10:g.17476966G>C

gnomAD frequency: 0.00001  dbSNP: rs1395224084

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001851771	SCV002200503	uncertain significance	not provided	2021-12-19	criteria provided, single submitter	clinical testing	This variant occurs in a non-coding region of the ABCC8 gene. It does not change the encoded amino acid sequence of the ABCC8 protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with hyperinsulinism of infancy with diffuse pathology but a second variant was not observed in maternal allele (PMID: 15579781). This variant is also known as -64C>G. Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects ABCC8 function (PMID: 15579781). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002254260	SCV002524161	uncertain significance	Maturity onset diabetes mellitus in young		criteria provided, single submitter	research	Mutations in ABCC8 gene are associated with both neonatal diabetes mellitus as well as MODY. Patients with this mutation may have a better response to sulfonylureas. However, no sufficient evidence is found to ascertain the role of this particular variant ( rs1395224084) in MODY yet.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002254261	SCV002524162	uncertain significance	Transitory neonatal diabetes mellitus		criteria provided, single submitter	research	Mutations in ABCC8 gene are associated with both neonatal diabetes mellitus as well as MODY. Patients with this mutation may have a better response to sulfonylureas. However, no sufficient evidence is found to ascertain the role of this particular variant ( rs1395224084) in neonatal diabetes yet.
Fulgent Genetics, Fulgent Genetics	RCV005042022	SCV005676134	uncertain significance	Diabetes mellitus, transient neonatal, 2; Hyperinsulinemic hypoglycemia, familial, 1; Leucine-induced hypoglycemia; Type 2 diabetes mellitus; Diabetes mellitus, permanent neonatal 3	2024-02-28	criteria provided, single submitter	clinical testing
OMIM	RCV000009669	SCV000029887	pathogenic	Hyperinsulinemic hypoglycemia, familial, 1	2004-12-01	no assertion criteria provided	literature only
PreventionGenetics, part of Exact Sciences	RCV004734507	SCV005346298	uncertain significance	ABCC8-related disorder	2024-07-03	no assertion criteria provided	clinical testing	The ABCC8 c.-190C>G variant is located in the 5' untranslated region. This variant (also described as -64C>G) has been reported in an individual with hyperinsulinism of infancy (Tornovsky et al. 2004. PubMed ID: 15579781). An in vitro luciferase reporter assay found that this variant reduced transcription levels to only ~40% relative to the wild type promoter (Tornovsky et al. 2004. PubMed ID: 15579781). This variant has not been reported in the gnomAD database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.