Submissions for variant NM_000352.6(ABCC8):c.394T>C (p.Phe132Leu)

dbSNP: rs80356637

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001851772	SCV002247442	pathogenic	not provided	2021-01-19	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. 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. This variant has been observed in individual(s) with autosomal dominant permanent neonatal diabetes mellitus (PMID: 16613899). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 9102). This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with leucine at codon 132 of the ABCC8 protein (p.Phe132Leu). The phenylalanine residue is moderately conserved and there is a small physicochemical difference between phenylalanine and leucine.
Molecular Genetics, Madras Diabetes Research Foundation	RCV002051781	SCV002318403	likely pathogenic	Neonatal diabetes mellitus		criteria provided, single submitter	clinical testing
OMIM	RCV000009670	SCV000029888	pathogenic	Diabetes mellitus, permanent neonatal 3	2006-06-01	no assertion criteria provided	literature only
GeneReviews	RCV000020286	SCV000040645	not provided	Permanent neonatal diabetes mellitus		no assertion provided	literature only