NM_007078.3(LDB3):c.794G>A (p.Arg265His) AND not provided

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(2) (Last evaluated: Jul 1, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000183529.3

Allele description [Variation Report for NM_007078.3(LDB3):c.794G>A (p.Arg265His)]

NM_007078.3(LDB3):c.794G>A (p.Arg265His)

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.794G>A (p.Arg265His)
Other names:
p.R265H:CGC>CAC
HGVS:
  • NC_000010.11:g.86692000G>A
  • NG_008876.1:g.28437G>A
  • NM_001080114.2:c.653G>A
  • NM_001080115.2:c.794G>A
  • NM_001080116.1:c.653G>A
  • NM_001171610.2:c.998G>A
  • NM_001171611.2:c.998G>A
  • NM_001368063.1:c.794G>A
  • NM_001368064.1:c.794G>A
  • NM_001368065.1:c.794G>A
  • NM_001368066.1:c.653G>A
  • NM_001368067.1:c.653G>A
  • NM_001368068.1:c.653G>A
  • NM_007078.3:c.794G>AMANE SELECT
  • NP_001073583.1:p.Arg218His
  • NP_001073584.1:p.Arg265His
  • NP_001073585.1:p.Arg218His
  • NP_001165081.1:p.Arg333His
  • NP_001165082.1:p.Arg333His
  • NP_001354992.1:p.Arg265His
  • NP_001354993.1:p.Arg265His
  • NP_001354994.1:p.Arg265His
  • NP_001354995.1:p.Arg218His
  • NP_001354996.1:p.Arg218His
  • NP_001354997.1:p.Arg218His
  • NP_009009.1:p.Arg265His
  • LRG_385t1:c.794G>A
  • LRG_385t2:c.653G>A
  • LRG_385:g.28437G>A
  • LRG_385p2:p.Arg218His
  • NC_000010.10:g.88451757G>A
  • NM_007078.2:c.794G>A
Protein change:
R218H
Links:
dbSNP: rs45458895
NCBI 1000 Genomes Browser:
rs45458895
Molecular consequence:
  • NM_001080114.2:c.653G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001080115.2:c.794G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001080116.1:c.653G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001171610.2:c.998G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001171611.2:c.998G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368063.1:c.794G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368064.1:c.794G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368065.1:c.794G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368066.1:c.653G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368067.1:c.653G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368068.1:c.653G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007078.3:c.794G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000235996GeneDxcriteria provided, single submitter
Uncertain significance
(Apr 2, 2014)
germlineclinical testing

Citation Link,

SCV001004605Invitaecriteria provided, single submitter
Likely benign
(Jan 2, 2019)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001502622CeGaT Praxis fuer Humangenetik Tuebingencriteria provided, single submitter
Uncertain significance
(Jul 1, 2020)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineyes1not providednot providednot providednot providedclinical testing

Citations

PubMed

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 GeneDx, SCV000235996.9

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

p.Arg265His (CGC>CAC): c.794 G>A in exon 5 of the LDB3 gene (NM_007078.2). The R265H variant in the LDB3 gene has not been reported previously as a disease-causing mutation or as a benign polymorphism to our knowledge. Although R265H results in a conservative amino acid substitution of one positively charged residue for another, the substitution occurs at a residue that is conserved across species. A mutation affecting a nearby residue (R268C) has been reported in association with myofibrillar myopathy. The R265H variant has been reported in dbSNP in 1/366 control chromosomes, however it was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in DCM,CARDIOMYOPATHY panel(s).

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

From Invitae, SCV001004605.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From CeGaT Praxis fuer Humangenetik Tuebingen, SCV001502622.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Jul 29, 2021

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