NM_007078.3(LDB3):c.59dup (p.Lys21fs) AND Myofibrillar myopathy 4

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 11, 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:: RCV003504502.2

Allele description [Variation Report for NM_007078.3(LDB3):c.59dup (p.Lys21fs)]

NM_007078.3(LDB3):c.59dup (p.Lys21fs)

Gene:

LDB3:LIM domain binding 3 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

10q23.2

Genomic location:

Preferred name:

NM_007078.3(LDB3):c.59dup (p.Lys21fs)

HGVS:

NC_000010.11:g.86668750dup
NG_008876.1:g.5187dup
NG_183689.1:g.209dup
NM_001080114.2:c.59dup
NM_001080115.2:c.59dup
NM_001080116.1:c.59dup
NM_001171610.2:c.59dup
NM_001171611.2:c.59dup
NM_001368063.1:c.59dup
NM_001368064.1:c.59dup
NM_001368065.1:c.59dup
NM_001368066.1:c.59dup
NM_001368067.1:c.59dup
NM_001368068.1:c.59dup
NM_007078.3:c.59dupMANE SELECT
NP_001073583.1:p.Lys21fs
NP_001073584.1:p.Lys21fs
NP_001073585.1:p.Lys21fs
NP_001165081.1:p.Lys21fs
NP_001165082.1:p.Lys21fs
NP_001354992.1:p.Lys21fs
NP_001354993.1:p.Lys21fs
NP_001354994.1:p.Lys21fs
NP_001354995.1:p.Lys21fs
NP_001354996.1:p.Lys21fs
NP_001354997.1:p.Lys21fs
NP_009009.1:p.Lys21Glnfs
NP_009009.1:p.Lys21fs
LRG_385t1:c.59dup
LRG_385t2:c.59dup
LRG_385:g.5187dup
LRG_385p1:p.Lys21Glnfs
LRG_385p2:p.Lys21fs
NC_000010.10:g.88428501_88428502insG
NC_000010.10:g.88428507dup
NM_007078.2:c.59dup

Protein change:

K21fs

Molecular consequence:

NM_001080114.2:c.59dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001080115.2:c.59dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001080116.1:c.59dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001171610.2:c.59dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001171611.2:c.59dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001368063.1:c.59dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001368064.1:c.59dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001368065.1:c.59dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001368066.1:c.59dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001368067.1:c.59dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001368068.1:c.59dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_007078.3:c.59dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Myofibrillar myopathy 4
Synonyms:: Myofibrillar myopathy, ZASP-related; Zaspopathy (type)
Identifiers:: MONDO: MONDO:0012277; MedGen: C4721886; OMIM: 609452

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004292343	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 11, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 36253531, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004292343

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 11, 2023)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Biallelic loss of LDB3 leads to a lethal pediatric dilated cardiomyopathy.

Koopmann TT, Jamshidi Y, Naghibi-Sistani M, van der Klift HM, Birjandi H, Al-Hassnan Z, Alwadai A, Zifarelli G, Karimiani EG, Sedighzadeh S, Bahreini A, Nouri N, Peter M, Watanabe K, van Duyvenvoorde HA, Ruivenkamp CAL, Teunissen AKK, Ten Harkel ADJ, van Duinen SG, Haak MC, Prada CE, Santen GWE, et al.

Eur J Hum Genet. 2023 Jan;31(1):97-104. doi: 10.1038/s41431-022-01204-9. Epub 2022 Oct 17.

PubMed [citation]

PMID:: 36253531
PMCID:: PMC9823012

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004292343.1

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

Description

The LDB3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_007078.3, which corresponds to the same sequence change NM_001080116.1:c.59dup in the primary transcript. This sequence change creates a premature translational stop signal (p.Lys21Glnfs*27) in the LDB3 gene. It is expected to result in an absent or disrupted protein product in both transcripts. However, loss-of-function variants in LDB3 are only known to be pathogenic in the alternate transcript (PMID: 36253531). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with LDB3-related conditions. For these reasons, this variant has been 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: Sep 29, 2024

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