NM_001308120.2(TOGARAM1):c.1084C>T (p.Gln362Ter) AND Joubert syndrome 37

Clinical significance:Pathogenic (Last evaluated: Feb 22, 2021)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001293023.1

Allele description [Variation Report for NM_001308120.2(TOGARAM1):c.1084C>T (p.Gln362Ter)]

NM_001308120.2(TOGARAM1):c.1084C>T (p.Gln362Ter)

Gene:
TOGARAM1:TOG array regulator of axonemal microtubules 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q21.2
Genomic location:
Preferred name:
NM_001308120.2(TOGARAM1):c.1084C>T (p.Gln362Ter)
HGVS:
  • NC_000014.9:g.44963505C>T
  • NM_001308120.2:c.1084C>TMANE SELECT
  • NM_015091.4:c.1084C>T
  • NP_001295049.1:p.Gln362Ter
  • NP_055906.2:p.Gln362Ter
  • NC_000014.8:g.45432708C>T
  • NM_015091.2:c.1084C>T
  • NR_131765.2:n.1316C>T
Protein change:
Q362*; GLN362TER
Links:
OMIM: 617618.0003
Molecular consequence:
  • NR_131765.2:n.1316C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_001308120.2:c.1084C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_015091.4:c.1084C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Joubert syndrome 37
Identifiers:
MONDO: MONDO:0030933; MedGen: CN295300; OMIM: 619185

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001481795OMIMno assertion criteria providedPathogenic
(Feb 22, 2021)
germlineliterature only

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Dysfunction of the ciliary ARMC9/TOGARAM1 protein module causes Joubert syndrome.

Latour BL, Van De Weghe JC, Rusterholz TD, Letteboer SJ, Gomez A, Shaheen R, Gesemann M, Karamzade A, Asadollahi M, Barroso-Gil M, Chitre M, Grout ME, van Reeuwijk J, van Beersum SE, Miller CV, Dempsey JC, Morsy H; University of Washington Center for Mendelian Genomics., Bamshad MJ; Genomics England Research Consortium., Nickerson DA, Neuhauss SC, et al.

J Clin Invest. 2020 Aug 3;130(8):4423-4439. doi: 10.1172/JCI131656.

PubMed [citation]
PMID:
32453716
PMCID:
PMC7410078

Details of each submission

From OMIM, SCV001481795.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a 16-year-old boy (UW360-3) with Joubert syndrome-37 (JBTS37; 619185) Latour et al. (2020) identified compound heterozygous mutations in the TOGARAM1 gene: a c.1084C-T transition (c.1084C-T, NM_015091.2), resulting in a gln362-to-ter (Q362X) substitution in the TOG2 domain, and a 12-kb intragenic deletion, resulting in the deletion of exons 4-7 (617618.0004). The mutations, which were found by exome sequencing, were each inherited from an unaffected parent. Neither was present in the gnomAD database. Patient fibroblasts showed slightly shorter cilia length compared to controls (2.6 versus 3.0 micrometers) and a slightly lower ciliation rate compared to controls (85% versus 91%). Further detailed studies of patient fibroblasts and ciliated cells from mutant zebrafish showed reduced acetylation and polyglutamylation of axonemal microtubules compared to controls, indicating impaired posttranslational modification of tubulin, as well as abnormal ciliary stability.

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

Last Updated: Jun 14, 2021

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