NM_007078.3(LDB3):c.1457dup (p.Ser486fs) AND Myofibrillar myopathy 4

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 13, 2019
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:: RCV001248403.8

Allele description [Variation Report for NM_007078.3(LDB3):c.1457dup (p.Ser486fs)]

NM_007078.3(LDB3):c.1457dup (p.Ser486fs)

Gene:

LDB3:LIM domain binding 3 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

10q23.2

Genomic location:

Preferred name:

NM_007078.3(LDB3):c.1457dup (p.Ser486fs)

HGVS:

NC_000010.11:g.86716552dup
NG_008876.1:g.52989dup
NM_001080114.2:c.1127dup
NM_001171610.2:c.1472dup
NM_001368064.1:c.1268dup
NM_001368065.1:c.1268dup
NM_001368066.1:c.1316dup
NM_007078.3:c.1457dupMANE SELECT
NP_001073583.1:p.Ser376fs
NP_001165081.1:p.Ser491fs
NP_001354993.1:p.Ser423fs
NP_001354994.1:p.Ser423fs
NP_001354995.1:p.Ser439fs
NP_009009.1:p.Ser486fs
LRG_385t1:c.1457dup
LRG_385:g.52989dup
NC_000010.10:g.88476308_88476309insG
NC_000010.10:g.88476309dup
NM_007078.2:c.1457dup

Protein change:

S376fs

Links:

dbSNP: rs1846883652

NCBI 1000 Genomes Browser:

rs1846883652

Molecular consequence:

NM_001080114.2:c.1127dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001171610.2:c.1472dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001368064.1:c.1268dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001368065.1:c.1268dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001368066.1:c.1316dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_007078.3:c.1457dup - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV001421887	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 13, 2019)	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

SCV001421887

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 13, 2019)

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, SCV001421887.4

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

Description

This sequence change creates a premature translational stop signal (p.Ser486Argfs*9) in the LDB3 gene. It is expected to result in an absent or disrupted protein product.¬†The LDB3 gene has multiple clinically relevant transcripts. The¬†p.Ser486Argfs*9¬†variant occurs in alternate transcript NM_007078.2, which corresponds to c.*17178dup in NM_001080116.1, the primary transcript listed in the Methods. 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. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in LDB3 cause disease. This variant has not been reported in the literature in individuals with LDB3-related conditions. This variant is not present in population databases (ExAC no frequency).

#	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: Sep 29, 2024

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