Submissions for variant NM_000817.3(GAD1):c.682A>C (p.Ile228Leu)

gnomAD frequency: 0.00040  dbSNP: rs45566933

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001836784	SCV000419231	uncertain significance	Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities	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.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000422631	SCV000510870	uncertain significance	not provided	2017-02-03	criteria provided, single submitter	clinical testing	Converted during submission to Uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001836784	SCV001560306	likely benign	Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities	2024-11-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002523093	SCV003539360	uncertain significance	Inborn genetic diseases	2022-08-05	criteria provided, single submitter	clinical testing	The c.682A>C (p.I228L) alteration is located in exon 7 (coding exon 6) of the GAD1 gene. This alteration results from a A to C substitution at nucleotide position 682, causing the isoleucine (I) at amino acid position 228 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen	RCV000422631	SCV004042093	likely benign	not provided	2023-09-01	criteria provided, single submitter	clinical testing	GAD1: BS1