Submissions for variant NM_000352.6(ABCC8):c.4532T>C (p.Ile1511Thr)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003062338	SCV003439614	pathogenic	not provided	2021-12-08	criteria provided, single submitter	clinical testing	Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ABCC8 protein function. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ile1511 amino acid residue in ABCC8. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects ABCC8 function (PMID: 18596924). This variant is also known as p.I1512T. This missense change has been observed in individual(s) with autosomal dominant congenital hyperinsulinism (PMID: 18596924). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1511 of the ABCC8 protein (p.Ile1511Thr).
Department of Endocrinology, Genetics and Metabolism, Shanghai Children's Medical Center	RCV003227081	SCV003922074	likely pathogenic	Hyperinsulinemic hypoglycemia, familial, 1		no assertion criteria provided	clinical testing