Submissions for variant NM_004006.3(DMD):c.2117C>A (p.Pro706Gln)

gnomAD frequency: 0.00004  dbSNP: rs781015830

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV001239735	SCV000221631	uncertain significance	Duchenne muscular dystrophy	2024-06-08	criteria provided, single submitter	research	Downgraded variant due to updated local frequency
Eurofins Ntd Llc (ga)	RCV000171433	SCV000226623	uncertain significance	not provided	2014-06-17	criteria provided, single submitter	clinical testing
GeneDx	RCV000259130	SCV000723864	likely benign	not specified	2017-10-25	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Laboratory Services, Illumina	RCV001168818	SCV001331446	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	RCV001239735	SCV001412630	likely benign	Duchenne muscular dystrophy	2024-11-26	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002415727	SCV002725275	uncertain significance	Cardiovascular phenotype	2023-11-20	criteria provided, single submitter	clinical testing	The p.P706Q variant (also known as c.2117C>A), located in coding exon 17 of the DMD gene, results from a C to A substitution at nucleotide position 2117. The proline at codon 706 is replaced by glutamine, an amino acid with similar properties. Based on data from gnomAD, the A allele has an overall frequency of 0.003% (6/182983) total alleles studied, with 3 hemizygotes observed. The highest observed frequency was 0.01% (2/19059) of South Asian alleles. This amino acid position is well 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.
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV001239735	SCV004807245	likely benign	Duchenne muscular dystrophy	2024-03-26	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004539577	SCV004759688	likely benign	DMD-related disorder	2023-09-28	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).