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NM_001376.5(DYNC1H1):c.751C>T (p.Arg251Cys) AND Inborn genetic diseases

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Feb 8, 2024
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:
RCV001266345.7

Allele description [Variation Report for NM_001376.5(DYNC1H1):c.751C>T (p.Arg251Cys)]

NM_001376.5(DYNC1H1):c.751C>T (p.Arg251Cys)

Gene:
DYNC1H1:dynein cytoplasmic 1 heavy chain 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q32.31
Genomic location:
Preferred name:
NM_001376.5(DYNC1H1):c.751C>T (p.Arg251Cys)
HGVS:
  • NC_000014.9:g.101979951C>T
  • NG_008777.1:g.20424C>T
  • NM_001376.5:c.751C>TMANE SELECT
  • NP_001367.2:p.Arg251Cys
  • NC_000014.8:g.102446288C>T
  • NM_001376.4:c.751C>T
Protein change:
R251C
Links:
dbSNP: rs879253979
NCBI 1000 Genomes Browser:
rs879253979
Molecular consequence:
  • NM_001376.5:c.751C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Inborn genetic diseases
Identifiers:
MeSH: D030342; MedGen: C0950123

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001444519Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Feb 8, 2024) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

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

Citations

PubMed

Application of targeted multi-gene panel testing for the diagnosis of inherited peripheral neuropathy provides a high diagnostic yield with unexpected phenotype-genotype variability.

Antoniadi T, Buxton C, Dennis G, Forrester N, Smith D, Lunt P, Burton-Jones S.

BMC Med Genet. 2015 Sep 21;16:84. doi: 10.1186/s12881-015-0224-8.

PubMed [citation]
PMID:
26392352
PMCID:
PMC4578331

Clinical application of whole-exome sequencing across clinical indications.

Retterer K, Juusola J, Cho MT, Vitazka P, Millan F, Gibellini F, Vertino-Bell A, Smaoui N, Neidich J, Monaghan KG, McKnight D, Bai R, Suchy S, Friedman B, Tahiliani J, Pineda-Alvarez D, Richard G, Brandt T, Haverfield E, Chung WK, Bale S.

Genet Med. 2016 Jul;18(7):696-704. doi: 10.1038/gim.2015.148. Epub 2015 Dec 3.

PubMed [citation]
PMID:
26633542
See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV001444519.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

The c.751C>T (p.R251C) alteration is located in coding exon 4 of the DYNC1H1 gene. This alteration results from a C to T substitution at nucleotide position 751, causing the arginine (R) at amino acid position 251 to be replaced by a cysteine (C). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been determined to be the result of a de novo mutation in multiple individuals with features consistent with spinal muscular atrophy (Chan, 2018; Fernández Perrone, 2022). This alteration was also reported in a patient with an unspecified abnormality of the nervous system (Retterer, 2016). Two other alterations at the same codon, c.752G>A (p.R251H) and c.752G>T (p.R251L), have been detected in patients with features consistent with DYNC1H1-related neurologic disorders (Antoniadi, 2015; Derksen, 2021). The p.R251 amino acid is conserved in available vertebrate species. This missense alteration is located in a region that has a low rate of benign missense variation (Lek, 2016; Firth, 2009). The in silico prediction for the p.R251C alteration is inconclusive. Based on the available evidence, this alteration is classified as pathogenic.

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

Last Updated: Jun 22, 2025