Submissions for variant NM_000352.6(ABCC8):c.4090G>A (p.Val1364Ile)

dbSNP: rs138642224

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000296366	SCV000369251	uncertain significance	Permanent neonatal diabetes mellitus	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000349002	SCV000369252	uncertain significance	Hyperinsulinemic hypoglycemia, familial, 1	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000387248	SCV000369253	benign	Diabetes mellitus, transient neonatal, 2	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Athena Diagnostics Inc	RCV000710383	SCV000840593	uncertain significance	not provided	2019-09-30	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV001820891	SCV002071580	uncertain significance	not specified	2021-02-03	criteria provided, single submitter	clinical testing	This sequence change does not appear to have been previously described in patients with ABCC8-related disorders and has been described in the gnomAD database with a population frequency of 0.14% in African subpopulations (dbSNP rs138642224). The p.Val1364Ile change affects a highly conserved amino acid residue located in a domain of the ABCC8 protein that is known to be functional. The p.Val1364Ile substitution appears to be possibly benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Val1364Ile change remains unknown at this time.
Invitae	RCV000710383	SCV002377765	likely benign	not provided	2024-01-16	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001833441	SCV002077538	uncertain significance	Hereditary hyperinsulinism	2019-11-11	no assertion criteria provided	clinical testing