NM_001308120.2(TOGARAM1):c.1124T>C (p.Leu375Pro) 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:
RCV001293021.1

Allele description [Variation Report for NM_001308120.2(TOGARAM1):c.1124T>C (p.Leu375Pro)]

NM_001308120.2(TOGARAM1):c.1124T>C (p.Leu375Pro)

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.1124T>C (p.Leu375Pro)
HGVS:
  • NC_000014.9:g.44963545T>C
  • NM_001308120.2:c.1124T>CMANE SELECT
  • NM_015091.4:c.1124T>C
  • NP_001295049.1:p.Leu375Pro
  • NP_055906.2:p.Leu375Pro
  • NC_000014.8:g.45432748T>C
  • NM_015091.2:c.1124T>C
  • NR_131765.2:n.1356T>C
Protein change:
L375P; LEU375PRO
Links:
OMIM: 617618.0001
Molecular consequence:
  • NM_001308120.2:c.1124T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_015091.4:c.1124T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_131765.2:n.1356T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV001481793OMIMno 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, SCV001481793.1

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

Description

In a 21-week-old fetus (UW351-3) with Joubert syndrome-37 (JBTS37; 619185), Latour et al. (2020) identified compound heterozygous missense mutations in the TOGARAM1 gene: a c.1124T-C transition (c.1124T-C, NM_015091.2), resulting in a leu375-to-pro (L375P) substitution at a highly conserved residue in the TOG2 domain, and a c.3931C-T transition, resulting in an arg1311-to-cys (R1311C; 617618.0002) substitution at a highly conserved residue in the TOG3 domain. The mutations, which were found by exome sequencing, were each inherited from an unaffected parent. L375P was present at a low frequency in the gnomAD database (8 of 276,914 alleles), whereas R1311C was not present. Studies of patient cells were not performed, but functional expression studies in transfected TOGARAM1-null RPE cells showed that L375P resulted in longer cilia, whereas R1311C resulted in shorter cilia, compared to controls. L375P abolished the interaction between TOGARAM1 and ARMC9 (617612), whereas R1311C did not influence this interaction.

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

Last Updated: Jun 14, 2021

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