NM_004006.3(DMD):c.4996C>T (p.Arg1666Ter) AND Qualitative or quantitative defects of dystrophin

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 21, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003323389.2

Allele description [Variation Report for NM_004006.3(DMD):c.4996C>T (p.Arg1666Ter)]

NM_004006.3(DMD):c.4996C>T (p.Arg1666Ter)

Gene:

DMD:dystrophin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp21.1

Genomic location:

Preferred name:

NM_004006.3(DMD):c.4996C>T (p.Arg1666Ter)

Other names:

NP_003997.1:p.Arg1666*

HGVS:

NC_000023.11:g.32365049G>A
NG_012232.1:g.979561C>T
NM_000109.4:c.4972C>T
NM_004006.3:c.4996C>TMANE SELECT
NM_004009.3:c.4984C>T
NM_004010.3:c.4627C>T
NM_004011.4:c.973C>T
NM_004012.4:c.964C>T
NP_000100.3:p.Arg1658Ter
NP_003997.1:p.Arg1666Ter
NP_003997.2:p.Arg1666Ter
NP_004000.1:p.Arg1662Ter
NP_004001.1:p.Arg1543Ter
NP_004002.3:p.Arg325Ter
NP_004003.2:p.Arg322Ter
LRG_199t1:c.4996C>T
LRG_199:g.979561C>T
LRG_199p1:p.Arg1666Ter
NC_000023.10:g.32383166G>A
NM_004006.2:c.4996C>T
NM_004006.3:c.4996C>T

Protein change:

R1543*

Links:

dbSNP: rs398123973

NCBI 1000 Genomes Browser:

rs398123973

Molecular consequence:

NM_000109.4:c.4972C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004006.3:c.4996C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004009.3:c.4984C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004010.3:c.4627C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004011.4:c.973C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004012.4:c.964C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Qualitative or quantitative defects of dystrophin
Identifiers:: MONDO: MONDO:0016147; MedGen: C5679787

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004029848	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Jul 21, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19760747, 21396098, 15351422 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004029848

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Jul 21, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Exon skipping-mediated dystrophin reading frame restoration for small mutations.

Spitali P, Rimessi P, Fabris M, Perrone D, Falzarano S, Bovolenta M, Trabanelli C, Mari L, Bassi E, Tuffery S, Gualandi F, Maraldi NM, Sabatelli-Giraud P, Medici A, Merlini L, Ferlini A.

Hum Mutat. 2009 Nov;30(11):1527-34. doi: 10.1002/humu.21092.

PubMed [citation]

PMID:: 19760747

Clinical and molecular characterization of a cohort of patients with novel nucleotide alterations of the Dystrophin gene detected by direct sequencing.

Magri F, Del Bo R, D'Angelo MG, Govoni A, Ghezzi S, Gandossini S, Sciacco M, Ciscato P, Bordoni A, Tedeschi S, Fortunato F, Lucchini V, Cereda M, Corti S, Moggio M, Bresolin N, Comi GP.

BMC Med Genet. 2011 Mar 11;12:37. doi: 10.1186/1471-2350-12-37.

PubMed [citation]

PMID:: 21396098
PMCID:: PMC3061890

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004029848.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: DMD c.4996C>T (p.Arg1666X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Variants downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 183156 control chromosomes (gnomAD). c.4996C>T has been reported in the literature in individuals affected with Dystrophinopathies (example: Tuffery-Giraud_2004, Spitali_2009, and Magri_2011). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 10, 2024

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