NM_007078.3(LDB3):c.690-4811C>T AND Myofibrillar myopathy, ZASP-related

Clinical significance:Uncertain significance (Last evaluated: Feb 15, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000815119.3

Allele description [Variation Report for NM_007078.3(LDB3):c.690-4811C>T]

NM_007078.3(LDB3):c.690-4811C>T

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_007078.3(LDB3):c.690-4811C>T
HGVS:
  • NC_000010.11:g.86687085C>T
  • NG_008876.1:g.23522C>T
  • NG_054099.1:g.3114C>T
  • NM_001080114.2:c.361C>T
  • NM_001080115.2:c.690-4811C>T
  • NM_001080116.1:c.361C>T
  • NM_001171610.2:c.706C>T
  • NM_001171611.2:c.706C>T
  • NM_001368063.1:c.690-4811C>T
  • NM_001368064.1:c.690-4811C>T
  • NM_001368065.1:c.690-4811C>T
  • NM_001368066.1:c.361C>T
  • NM_001368067.1:c.361C>T
  • NM_001368068.1:c.361C>T
  • NM_007078.3:c.690-4811C>TMANE SELECT
  • NP_001073583.1:p.Arg121Cys
  • NP_001073585.1:p.Arg121Cys
  • NP_001165081.1:p.Arg236Cys
  • NP_001165082.1:p.Arg236Cys
  • NP_001354995.1:p.Arg121Cys
  • NP_001354996.1:p.Arg121Cys
  • NP_001354997.1:p.Arg121Cys
  • LRG_385t2:c.361C>T
  • LRG_385:g.23522C>T
  • LRG_385p2:p.Arg121Cys
  • NC_000010.10:g.88446842C>T
Protein change:
R121C
Links:
dbSNP: rs750606592
NCBI 1000 Genomes Browser:
rs750606592
Molecular consequence:
  • NM_001080115.2:c.690-4811C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001368063.1:c.690-4811C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001368064.1:c.690-4811C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001368065.1:c.690-4811C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007078.3:c.690-4811C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001080114.2:c.361C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001080116.1:c.361C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001171610.2:c.706C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001171611.2:c.706C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368066.1:c.361C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368067.1:c.361C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368068.1:c.361C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Myofibrillar myopathy, ZASP-related (MFM4)
Synonyms:
MYOPATHY, MYOFIBRILLAR, 4; Zaspopathy (type)
Identifiers:
MONDO: MONDO:0012277; MedGen: C4721886; OMIM: 609452

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000955564Invitaecriteria provided, single submitter
Uncertain significance
(Feb 15, 2020)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot 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 Invitae, SCV000955564.3

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

Description

This sequence change replaces arginine with cysteine at codon 121 of the LDB3 protein (p.Arg121Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs750606592, ExAC 0.002%). This variant has not been reported in the literature in individuals with LDB3-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Mar 7, 2021

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