Submissions for variant NM_004006.3(DMD):c.9338G>A (p.Arg3113Gln)

dbSNP: rs1556320083

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000554971	SCV000625986	benign	Duchenne muscular dystrophy	2024-11-24	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV000788497	SCV000927641	uncertain significance	not provided	2018-04-19	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002377000	SCV002686763	uncertain significance	Cardiovascular phenotype	2023-12-05	criteria provided, single submitter	clinical testing	The p.R3113Q variant (also known as c.9338G>A), located in coding exon 64 of the DMD gene, results from a G to A substitution at nucleotide position 9338. The arginine at codon 3113 is replaced by glutamine, an amino acid with highly similar properties. This variant has been detected in an individual from a dystrophinopathies cohort (Wang L et al. Front Genet, 2019 Feb;10:114). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV002470903	SCV002768082	uncertain significance	Dilated cardiomyopathy 3B	2022-02-02	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3B. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Duchenne muscular dystrophy (MIM#310200), Becker muscular dystrophy (MIM#300376), and dilated cardiomyopathy 3B (MIM#302045). (I) 0109 - This gene is associated with both X-linked recessive and dominant disease. This gene is primarily associated with X-linked recessive disease relating to the muscular dystrophy phenotypes but is also reported to be associated with X-linked dominant DCM (OMIM, PMID: 26066469). (I) 0200 - Variant is predicted to result in a missense amino acid change from arginine to glutamine. (I) 0253 - This variant is hemizygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0600 - Variant is located in the annotated EF-hand 2 domain (UniProt). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0809 - Previous evidence of pathogenicity for this variant is inconclusive. This variant has been reported in an individual with dystrophinopathies and has VUS entries in ClinVar and LOVD (PMID: 30833962). (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Baylor Genetics	RCV003470720	SCV004194011	likely pathogenic	Becker muscular dystrophy	2021-12-14	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001834740	SCV002080172	uncertain significance	Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency	2018-07-24	no assertion criteria provided	clinical testing