Submissions for variant NM_004006.3(DMD):c.1888A>G (p.Thr630Ala)

gnomAD frequency: 0.00124  dbSNP: rs72468692

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001704878	SCV000235829	likely benign	not provided	2019-12-27	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 24274981, 19937601)
Ambry Genetics	RCV000250253	SCV000319904	benign	Cardiovascular phenotype	2015-07-10	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Eurofins Ntd Llc (ga)	RCV000183383	SCV000337584	benign	not specified	2015-11-21	criteria provided, single submitter	clinical testing
Invitae	RCV000526900	SCV000625855	benign	Duchenne muscular dystrophy	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001165930	SCV001328188	likely benign	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000183383	SCV001448552	benign	not specified	2020-11-23	criteria provided, single submitter	clinical testing	Variant summary: DMD c.1888A>G (p.Thr630Ala) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0016 in 183238 control chromosomes. The observed variant frequency is approximately 144 fold of the estimated maximal expected allele frequency for a pathogenic variant in DMD causing Dystrophinopathies phenotype (1.1e-05), strongly suggesting that the variant is benign. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001704878	SCV003800446	benign	not provided	2022-04-27	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001833099	SCV002092219	likely benign	Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency	2019-06-24	no assertion criteria provided	clinical testing