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NM_007078.3(LDB3):c.655C>T (p.Arg219Ter) AND Myofibrillar myopathy 4

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 17, 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:
RCV001242445.7

Allele description [Variation Report for NM_007078.3(LDB3):c.655C>T (p.Arg219Ter)]

NM_007078.3(LDB3):c.655C>T (p.Arg219Ter)

Gene:
LDB3:LIM domain binding 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10q23.2
Genomic location:
Preferred name:
NM_007078.3(LDB3):c.655C>T (p.Arg219Ter)
HGVS:
  • NC_000010.11:g.86681769C>T
  • NG_008876.1:g.18206C>T
  • NM_001080114.2:c.321+1612C>T
  • NM_001080115.2:c.655C>T
  • NM_001080116.1:c.321+1612C>T
  • NM_001171610.2:c.655C>T
  • NM_001171611.2:c.655C>T
  • NM_001368063.1:c.655C>T
  • NM_001368064.1:c.655C>T
  • NM_001368065.1:c.655C>T
  • NM_001368066.1:c.321+1612C>T
  • NM_001368067.1:c.321+1612C>T
  • NM_001368068.1:c.321+1612C>T
  • NM_007078.3:c.655C>TMANE SELECT
  • NP_001073584.1:p.Arg219Ter
  • NP_001165081.1:p.Arg219Ter
  • NP_001165082.1:p.Arg219Ter
  • NP_001354992.1:p.Arg219Ter
  • NP_001354993.1:p.Arg219Ter
  • NP_001354994.1:p.Arg219Ter
  • NP_009009.1:p.Arg219Ter
  • LRG_385t1:c.655C>T
  • LRG_385t2:c.321+1612C>T
  • LRG_385:g.18206C>T
  • NC_000010.10:g.88441526C>T
  • NM_007078.2:c.655C>T
  • p.Arg219X
Protein change:
R219*
Links:
dbSNP: rs727503123
NCBI 1000 Genomes Browser:
rs727503123
Molecular consequence:
  • NM_001080114.2:c.321+1612C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001080116.1:c.321+1612C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001368066.1:c.321+1612C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001368067.1:c.321+1612C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001368068.1:c.321+1612C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001080115.2:c.655C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001171610.2:c.655C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001171611.2:c.655C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001368063.1:c.655C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001368064.1:c.655C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001368065.1:c.655C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_007078.3:c.655C>T - nonsense - [Sequence Ontology: SO:0001587]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001415532Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Aug 17, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001415532.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 163829). This variant has not been reported in the literature in individuals affected with LDB3-related conditions. This variant is present in population databases (rs727503123, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Arg219*) in the LDB3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LDB3 are known to be pathogenic (PMID: 36253531). The LDB3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_007078.3, and corresponds to NM_001080116.1:c.321+1612C>T in the primary transcript.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 1, 2024