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NM_001164508.2(NEB):c.24302_24305dup (p.Leu8102fs) AND Nemaline myopathy

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 26, 2017
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:
RCV000781649.1

Allele description [Variation Report for NM_001164508.2(NEB):c.24302_24305dup (p.Leu8102fs)]

NM_001164508.2(NEB):c.24302_24305dup (p.Leu8102fs)

Genes:
NEB:nebulin [Gene - OMIM - HGNC]
RIF1:replication timing regulatory factor 1 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
2q23.3
Genomic location:
Preferred name:
NM_001164508.2(NEB):c.24302_24305dup (p.Leu8102fs)
HGVS:
  • NC_000002.12:g.151497029_151497032dup
  • NG_009382.2:g.242456_242459dup
  • NM_001164507.2:c.24302_24305dup
  • NM_001164508.2:c.24302_24305dupMANE SELECT
  • NM_001271208.2:c.24407_24410dup
  • NM_004543.5:c.18826-664_18826-661dup
  • NP_001157979.2:p.Leu8102fs
  • NP_001157980.2:p.Leu8102fs
  • NP_001258137.2:p.Leu8137fs
  • LRG_202t1:c.24407_24410dup
  • LRG_202:g.242456_242459dup
  • NC_000002.11:g.152353542_152353543insAACA
  • NC_000002.11:g.152353543_152353546dup
  • NM_001271208.1:c.24407_24410dup
  • NM_001271208.1:c.24407_24410dupTGTT
Protein change:
L8102fs
Links:
dbSNP: rs1344099907
NCBI 1000 Genomes Browser:
rs1344099907
Molecular consequence:
  • NM_001164507.2:c.24302_24305dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001164508.2:c.24302_24305dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001271208.2:c.24407_24410dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_004543.5:c.18826-664_18826-661dup - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:
Nemaline myopathy
Synonyms:
Myopathies, Nemaline; Rod myopathy
Identifiers:
MONDO: MONDO:0018958; MedGen: C0206157; OMIM: PS161800

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000919861Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Pathogenic
(Dec 26, 2017)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

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

Citations

PubMed

Epigenetic changes as a common trigger of muscle weakness in congenital myopathies.

Rokach O, Sekulic-Jablanovic M, Voermans N, Wilmshurst J, Pillay K, Heytens L, Zhou H, Muntoni F, Gautel M, Nevo Y, Mitrani-Rosenbaum S, Attali R, Finotti A, Gambari R, Mosca B, Jungbluth H, Zorzato F, Treves S.

Hum Mol Genet. 2015 Aug 15;24(16):4636-47. doi: 10.1093/hmg/ddv195. Epub 2015 May 27.

PubMed [citation]
PMID:
26019235

Mutation update: the spectra of nebulin variants and associated myopathies.

Lehtokari VL, Kiiski K, Sandaradura SA, Laporte J, Repo P, Frey JA, Donner K, Marttila M, Saunders C, Barth PG, den Dunnen JT, Beggs AH, Clarke NF, North KN, Laing NG, Romero NB, Winder TL, Pelin K, Wallgren-Pettersson C.

Hum Mutat. 2014 Dec;35(12):1418-26. doi: 10.1002/humu.22693.

PubMed [citation]
PMID:
25205138
PMCID:
PMC4295925

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000919861.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Variant summary: The NEB c.24407_24410dupTGTT (p.Leu8137PhefsX18) variant results in a premature termination codon, predicted to cause a truncated or absent NEB protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g., p.Arg8187X and p.Pro8211fsX4). One in silico tool predicts a damaging outcome for this variant. This variant was found in 2/178594 control chromosomes at a frequency of 0.0000112, which does not exceed the estimated maximal expected allele frequency of a pathogenic NEB variant (0.0035355). In the literature, the variant has been reported in several patients and families with nemaline myopathy as both a compound heterozygous and homozygous allele. Taken together, this variant is classified as pathogenic.

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

Last Updated: Feb 1, 2025