NM_007078.3(LDB3):c.1609del (p.Gln537fs) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Oct 18, 2013)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000150927.1

Allele description [Variation Report for NM_007078.3(LDB3):c.1609del (p.Gln537fs)]

NM_007078.3(LDB3):c.1609del (p.Gln537fs)

Gene:
LDB3:LIM domain binding 3 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
10q23.2
Genomic location:
Preferred name:
NM_007078.3(LDB3):c.1609del (p.Gln537fs)
HGVS:
  • NC_000010.10:g.88476460del
  • NC_000010.11:g.86716704del
  • NG_008876.1:g.53141del
  • NM_001080114.2:c.1279del
  • NM_001171610.2:c.1624del
  • NM_001368064.1:c.1420del
  • NM_001368065.1:c.1420del
  • NM_001368066.1:c.1468del
  • NM_007078.3:c.1609delMANE SELECT
  • NP_001073583.1:p.Gln427fs
  • NP_001165081.1:p.Gln542fs
  • NP_001354993.1:p.Gln474fs
  • NP_001354994.1:p.Gln474fs
  • NP_001354995.1:p.Gln490fs
  • NP_009009.1:p.Gln537fs
  • LRG_385t1:c.1609del
  • LRG_385:g.53141del
  • NC_000010.10:g.88476460del
  • NC_000010.10:g.88476461del
  • NC_000010.10:g.88476461delC
  • NM_007078.2:c.1609delC
  • p.Gln537ArgfsX28
Protein change:
Q427fs
Links:
dbSNP: rs727503129
NCBI 1000 Genomes Browser:
rs727503129
Molecular consequence:
  • NM_001080114.2:c.1279del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001171610.2:c.1624del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001368064.1:c.1420del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001368065.1:c.1420del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001368066.1:c.1468del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_007078.3:c.1609del - frameshift variant - [Sequence Ontology: SO:0001589]
Observations:
1

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000198569Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Uncertain significance
(Oct 18, 2013)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided31not providednot providednot providedclinical testing

Citations

PubMed

Cardiac-specific ablation of Cypher leads to a severe form of dilated cardiomyopathy with premature death.

Zheng M, Cheng H, Li X, Zhang J, Cui L, Ouyang K, Han L, Zhao T, Gu Y, Dalton ND, Bang ML, Peterson KL, Chen J.

Hum Mol Genet. 2009 Feb 15;18(4):701-13. doi: 10.1093/hmg/ddn400. Epub 2008 Nov 21.

PubMed [citation]
PMID:
19028670
PMCID:
PMC2722217

Ablation of Cypher, a PDZ-LIM domain Z-line protein, causes a severe form of congenital myopathy.

Zhou Q, Chu PH, Huang C, Cheng CF, Martone ME, Knoll G, Shelton GD, Evans S, Chen J.

J Cell Biol. 2001 Nov 12;155(4):605-12. Epub 2001 Nov 5.

PubMed [citation]
PMID:
11696561
PMCID:
PMC2198871
See all PubMed Citations (3)

Details of each submission

From Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, SCV000198569.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testing PubMed (3)

Description

Variant classified as Uncertain Significance - Favor Pathogenic. The Gln537fs va riant in LDB3 has not been previously reported in any other families with cardio myopathy or in large European American or African American cohorts. This framesh ift variant is predicted to alter the protein?s amino acid sequence beginning at position 537 and lead to a premature termination codon 28 amino acids downstrea m. This alteration is then predicted to lead to a truncated or absent protein (l oss of function). Studies in mice have shown that the spectrum of phenotypes res ulting from homozygous loss of function of LDB3 includes DCM (Zheng 2009; heart specific loss of function) and congenital myopathy (Zhou 2001, complete loss of function). Our laboratory has previously identified one loss of function varian t in an individual with VT and SCA but overall, this type of variant has not yet been reported in individuals with cardio/myopathy. In summary, the predicted im pact to the protein increases the likelihood that this variant is pathogenic but additional studies are required to fully establish its clinical significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided3not provided1not provided

Last Updated: Sep 29, 2021

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