Submissions for variant NM_004006.3(DMD):c.6623A>G (p.Glu2208Gly)

gnomAD frequency: 0.00001  dbSNP: rs139937177

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001167893	SCV001330439	uncertain significance	Dilated cardiomyopathy 3B	2018-01-13	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001224835	SCV001397058	likely benign	Duchenne muscular dystrophy	2024-04-09	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002365820	SCV002663172	uncertain significance	Cardiovascular phenotype	2022-02-16	criteria provided, single submitter	clinical testing	The p.E2208G variant (also known as c.6623A>G), located in coding exon 46 of the DMD gene, results from an A to G substitution at nucleotide position 6623. The glutamic acid at codon 2208 is replaced by glycine, an amino acid with similar properties. Based on data from gnomAD, the G allele has an overall frequency of 0.001% (2/201795) total alleles studied, with 2 hemizygotes observed. The highest observed frequency was 0.002% (2/91038) of European (non-Finnish) alleles. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen	RCV003438705	SCV004164722	likely benign	not provided	2022-11-01	criteria provided, single submitter	clinical testing	DMD: BP4
Natera, Inc.	RCV001833726	SCV002087832	uncertain significance	Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency	2019-02-10	no assertion criteria provided	clinical testing