NM_004006.3(DMD):c.5582T>C (p.Leu1861Pro) AND Dilated cardiomyopathy 3B

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 24, 2022
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:: RCV002273324.3

Allele description [Variation Report for NM_004006.3(DMD):c.5582T>C (p.Leu1861Pro)]

NM_004006.3(DMD):c.5582T>C (p.Leu1861Pro)

Gene:

DMD:dystrophin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp21.1

Genomic location:

Preferred name:

NM_004006.3(DMD):c.5582T>C (p.Leu1861Pro)

HGVS:

NC_000023.11:g.32345947A>G
NG_012232.1:g.998663T>C
NM_000109.4:c.5558T>C
NM_004006.3:c.5582T>CMANE SELECT
NM_004009.3:c.5570T>C
NM_004010.3:c.5213T>C
NM_004011.4:c.1559T>C
NM_004012.4:c.1550T>C
NP_000100.3:p.Leu1853Pro
NP_003997.2:p.Leu1861Pro
NP_004000.1:p.Leu1857Pro
NP_004001.1:p.Leu1738Pro
NP_004002.3:p.Leu520Pro
NP_004003.2:p.Leu517Pro
LRG_199t1:c.5582T>C
LRG_199:g.998663T>C
NC_000023.10:g.32364064A>G
NM_004006.2:c.5582T>C

Protein change:

L1738P

Links:

dbSNP: rs2147030312

NCBI 1000 Genomes Browser:

rs2147030312

Molecular consequence:

NM_000109.4:c.5558T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_004006.3:c.5582T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_004009.3:c.5570T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_004010.3:c.5213T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_004011.4:c.1559T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_004012.4:c.1550T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Dilated cardiomyopathy 3B (CMD3B)
Synonyms:: CARDIOMYOPATHY, DILATED, X-LINKED; CMD3B: DMD-Related Dilated Cardiomyopathy
Identifiers:: MONDO: MONDO:0010542; MedGen: C3668940; Orphanet: 154; OMIM: 302045

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002557122	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 24, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26066469, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002557122

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jun 24, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

X-Linked Dilated Cardiomyopathy: A Cardiospecific Phenotype of Dystrophinopathy.

Nakamura A.

Pharmaceuticals (Basel). 2015 Jun 9;8(2):303-20. doi: 10.3390/ph8020303. Review.

PubMed [citation]

PMID:: 26066469
PMCID:: PMC4491663

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002557122.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

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 Becker muscular dystrophy (MIM#300376), Duchenne muscular dystrophy (MIM#310200) and dilated cardiomyopathy 3B (MIM#302045). (I) 0109 - This gene is associated with X-linked recessive disease, relating to the muscular dystrophy phenotypes. However, it is also associated with dilated cardiomyopathy, which can affect heterozygous females (OMIM, PMID: 26066469). (I) 0200 - Variant is predicted to result in a missense amino acid change from leucine to proline. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (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

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

Last Updated: Jul 23, 2024

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