Submissions for variant NM_000352.6(ABCC8):c.536A>G (p.Tyr179Cys)

dbSNP: rs919281813

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002530729	SCV003439710	pathogenic	not provided	2022-05-02	criteria provided, single submitter	clinical testing	This missense change has been observed in individual(s) with autosomal recessive diffuse or paternally inherited focal hyperinsulinism (PMID: 18796520, 20685672, 30352420). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. 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. ClinVar contains an entry for this variant (Variation ID: 552617). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 179 of the ABCC8 protein (p.Tyr179Cys).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV005056406	SCV005726279	uncertain significance	not specified	2024-11-15	criteria provided, single submitter	clinical testing	Variant summary: ABCC8 c.536A>G (p.Tyr179Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 233834 control chromosomes. c.536A>G has been reported in the literature in compound heterozygous individuals affected with Familial Hyperinsulinism (Damaj_2008, Xu_2018). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 18796520, 36239000, 30352420). ClinVar contains an entry for this variant (Variation ID: 552617). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Counsyl	RCV000667913	SCV000792438	uncertain significance	Hyperinsulinemic hypoglycemia, familial, 1	2017-06-27	no assertion criteria provided	clinical testing	This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact [e-mail].