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NM_001164508.2(NEB):c.23798T>C (p.Ile7933Thr) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Feb 24, 2022
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:
RCV001844268.1

Allele description [Variation Report for NM_001164508.2(NEB):c.23798T>C (p.Ile7933Thr)]

NM_001164508.2(NEB):c.23798T>C (p.Ile7933Thr)

Genes:
NEB:nebulin [Gene - OMIM - HGNC]
RIF1:replication timing regulatory factor 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q23.3
Genomic location:
Preferred name:
NM_001164508.2(NEB):c.23798T>C (p.Ile7933Thr)
HGVS:
  • NC_000002.12:g.151503386A>G
  • NG_009382.2:g.236102T>C
  • NM_001164507.2:c.23798T>C
  • NM_001164508.2:c.23798T>CMANE SELECT
  • NM_001271208.2:c.23903T>C
  • NM_004543.5:c.18695T>C
  • NP_001157979.2:p.Ile7933Thr
  • NP_001157980.2:p.Ile7933Thr
  • NP_001258137.2:p.Ile7968Thr
  • NP_004534.3:p.Ile6232Thr
  • LRG_202t1:c.23903T>C
  • LRG_202:g.236102T>C
  • NC_000002.11:g.152359900A>G
  • NC_000002.11:g.152359900A>G
  • NM_001271208.1:c.23903T>C
  • NM_004543.4:c.18695T>C
Protein change:
I6232T
Links:
dbSNP: rs140967744
NCBI 1000 Genomes Browser:
rs140967744
Molecular consequence:
  • NM_001164507.2:c.23798T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001164508.2:c.23798T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001271208.2:c.23903T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004543.5:c.18695T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV002103617Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Uncertain significance
(Feb 24, 2022)
germlineclinical testing

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

Citation Link

Summary from all submissions

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

Citations

PubMed

Optimized trio genome sequencing (OTGS) as a first-tier genetic test in critically ill infants: practice in China.

Wang H, Lu Y, Dong X, Lu G, Cheng G, Qian Y, Ni Q, Zhang P, Yang L, Wu B, Zhou W.

Hum Genet. 2020 Apr;139(4):473-482. doi: 10.1007/s00439-019-02103-8. Epub 2020 Jan 21.

PubMed [citation]
PMID:
31965297

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002103617.1

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

Description

Variant summary: NEB c.23903T>C (p.Ile7968Thr) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00015 in 249028 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in NEB causing Nemaline Myopathy 2 (0.00015 vs 0.0035), allowing no conclusion about variant significance. c.23903T>C has been reported in the literature as a VUS compound heterozygous genotype (with NEB, c.21340C>T) in at-least one critically ill infant affected with Pneumonia, Hernia, Global Developmental delay, Atelectasis and Dysphagia who underwent trio genome sequencing analysis (example, Wang_2020). The authors reported the diagnostic criteria as needing follow-up. These report(s) do not provide unequivocal conclusions about association of the variant with Nemaline Myopathy 2. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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

Last Updated: Jan 19, 2025