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NM_001368067.1(LDB3):c.494C>T (p.Ala165Val) AND Neuromuscular disease

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 21, 2018
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:
RCV000036847.6

Allele description [Variation Report for NM_001368067.1(LDB3):c.494C>T (p.Ala165Val)]

NM_001368067.1(LDB3):c.494C>T (p.Ala165Val)

Genes:
LDB3:LIM domain binding 3 [Gene - OMIM - HGNC]
LOC110121486:VISTA enhancer hs2143 [Gene]
Variant type:
single nucleotide variant
Cytogenetic location:
10q23.2
Genomic location:
Preferred name:
NM_001368067.1(LDB3):c.494C>T (p.Ala165Val)
HGVS:
  • NC_000010.11:g.86687218C>T
  • NG_008876.1:g.23655C>T
  • NG_054099.1:g.3247C>T
  • NM_001080114.2:c.494C>T
  • NM_001080115.2:c.690-4678C>T
  • NM_001080116.1:c.494C>T
  • NM_001171610.2:c.839C>T
  • NM_001171611.2:c.839C>T
  • NM_001368063.1:c.690-4678C>T
  • NM_001368064.1:c.690-4678C>T
  • NM_001368065.1:c.690-4678C>T
  • NM_001368066.1:c.494C>T
  • NM_001368067.1:c.494C>T
  • NM_001368068.1:c.494C>T
  • NM_007078.3:c.690-4678C>TMANE SELECT
  • NP_001073583.1:p.Ala165Val
  • NP_001073585.1:p.Ala165Val
  • NP_001165081.1:p.Ala280Val
  • NP_001165082.1:p.Ala280Val
  • NP_001354995.1:p.Ala165Val
  • NP_001354996.1:p.Ala165Val
  • NP_001354997.1:p.Ala165Val
  • LRG_385t1:c.690-4678C>T
  • LRG_385t2:c.494C>T
  • LRG_385:g.23655C>T
  • LRG_385p2:p.Ala165Val
  • NC_000010.10:g.88446975C>T
  • NM_001080114.1:c.494C>T
  • NM_007078.2:c.690-4678C>T
  • c.494C>T
Protein change:
A165V; ALA165VAL
Links:
OMIM: 605906.0002; dbSNP: rs121908334
NCBI 1000 Genomes Browser:
rs121908334
Molecular consequence:
  • NM_001080115.2:c.690-4678C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001368063.1:c.690-4678C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001368064.1:c.690-4678C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001368065.1:c.690-4678C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007078.3:c.690-4678C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001080114.2:c.494C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001080116.1:c.494C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001171610.2:c.839C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001171611.2:c.839C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368066.1:c.494C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368067.1:c.494C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368068.1:c.494C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Neuromuscular disease
Synonyms:
Neuromuscular Diseases; Neuromuscular disorder; Neuromyopathy
Identifiers:
MONDO: MONDO:0019056; MeSH: D009468; MedGen: C0027868

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000060502Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Pathogenic
(Nov 21, 2018) 		germlineclinical testing

PubMed (9)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical testing

Citations

PubMed

Impaired binding of ZASP/Cypher with phosphoglucomutase 1 is associated with dilated cardiomyopathy.

Arimura T, Inagaki N, Hayashi T, Shichi D, Sato A, Hinohara K, Vatta M, Towbin JA, Chikamori T, Yamashina A, Kimura A.

Cardiovasc Res. 2009 Jul 1;83(1):80-8. doi: 10.1093/cvr/cvp119. Epub 2009 Apr 17.

PubMed [citation]
PMID:
19377068

Distinct muscle imaging patterns in myofibrillar myopathies.

Fischer D, Kley RA, Strach K, Meyer C, Sommer T, Eger K, Rolfs A, Meyer W, Pou A, Pradas J, Heyer CM, Grossmann A, Huebner A, Kress W, Reimann J, Schröder R, Eymard B, Fardeau M, Udd B, Goldfarb L, Vorgerd M, Olivé M.

Neurology. 2008 Sep 2;71(10):758-65. doi: 10.1212/01.wnl.0000324927.28817.9b.

PubMed [citation]
PMID:
18765652
PMCID:
PMC2583436
See all PubMed Citations (9)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000060502.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (9)

Description

The p.Ala165Val variant in LDB3 has been reported in at least 6 individuals with myofibrillar myopathy and segregated with disease in 9 affected individuals fro m 1 family (Selcen 2005, Griggs 2007, Fischer 2008, Vincent 2016, LMM data). It has also been identified in 1/113280 of European chromosomes by gnomAD (http://g nomad.broadinstitute.org) and reported in ClinVar (Variant ID #4728). An in vitr o function study showed that this variant disrupted Ankrd2 binding (Martinelli 2 014) and a study of mouse myoblasts transfected with the p.Ala165Val mutation sh owed a disrution of Z-disc structure and an accumulation of F-actin (Lin 2014). In summary, this variant meets criteria to be classified as pathogenic for autos omal dominant myofibrillar myopathy. ACMG/AMP criteria applied: PP1_Strong, PM2, PS3_Moderate, PS4_Moderate.

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

Last Updated: Sep 29, 2024