NM_007078.3(LDB3):c.1546C>T (p.Arg516Trp) AND Myofibrillar myopathy 4

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 12, 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:: RCV001865546.4

Allele description [Variation Report for NM_007078.3(LDB3):c.1546C>T (p.Arg516Trp)]

NM_007078.3(LDB3):c.1546C>T (p.Arg516Trp)

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.1546C>T (p.Arg516Trp)

HGVS:

NC_000010.11:g.86716641C>T
NG_008876.1:g.53078C>T
NM_001080114.2:c.1216C>T
NM_001171610.2:c.1561C>T
NM_001368064.1:c.1357C>T
NM_001368065.1:c.1357C>T
NM_001368066.1:c.1405C>T
NM_007078.3:c.1546C>TMANE SELECT
NP_001073583.1:p.Arg406Trp
NP_001165081.1:p.Arg521Trp
NP_001354993.1:p.Arg453Trp
NP_001354994.1:p.Arg453Trp
NP_001354995.1:p.Arg469Trp
NP_009009.1:p.Arg516Trp
LRG_385t1:c.1546C>T
LRG_385:g.53078C>T
NC_000010.10:g.88476398C>T
NM_007078.2:c.1546C>T

Protein change:

R406W

Links:

dbSNP: rs773327911

NCBI 1000 Genomes Browser:

rs773327911

Molecular consequence:

NM_001080114.2:c.1216C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001171610.2:c.1561C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001368064.1:c.1357C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001368065.1:c.1357C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001368066.1:c.1405C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_007078.3:c.1546C>T - missense variant - [Sequence Ontology: SO:0001583]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002180529	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 12, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002180529

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 12, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002180529.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

The LDB3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_007078.3, and corresponds to NM_001080116.1:c.*17267C>T in the primary transcript. This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 516 of the LDB3 protein (p.Arg516Trp). This variant is present in population databases (rs773327911, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with LDB3-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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