NM_001082538.3(TCTN1):c.342-8A>G AND Joubert syndrome and related disorders

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jun 19, 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:: RCV004701124.1

Allele description [Variation Report for NM_001082538.3(TCTN1):c.342-8A>G]

NM_001082538.3(TCTN1):c.342-8A>G

Gene:

TCTN1:tectonic family member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q24.11

Genomic location:

Preferred name:

NM_001082538.3(TCTN1):c.342-8A>G

HGVS:

NC_000012.12:g.110626354A>G
NG_030381.1:g.17328A>G
NM_001082537.3:c.342-8A>G
NM_001082538.3:c.342-8A>GMANE SELECT
NM_001173975.3:c.174-8A>G
NM_001173976.2:c.162-8A>G
NM_001319680.2:c.342-8A>G
NM_001319681.2:c.-366-8A>G
NM_001319682.3:c.174-8A>G
NM_024549.6:c.342-8A>G
NC_000012.11:g.111064159A>G

Molecular consequence:

NM_001082537.3:c.342-8A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001082538.3:c.342-8A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001173975.3:c.174-8A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001173976.2:c.162-8A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001319680.2:c.342-8A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001319681.2:c.-366-8A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001319682.3:c.174-8A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_024549.6:c.342-8A>G - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Joubert syndrome and related disorders
Identifiers:: MONDO: MONDO:0015369; MedGen: C5679612

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005204635	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Jun 19, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005204635

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Jun 19, 2024)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

[Diagnosis of two cases from one family with Joubert syndrome caused by novel mutations of TCTN1 gene by whole exome sequencing].

Wang H, Jiang W, Dai M, Xiao B, Xu Y, Sun Y, Liu Y, Ying X, Sun Y, Wei W, Ji X.

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2019 Jul 10;36(7):686-689. doi: 10.3760/cma.j.issn.1003-9406.2019.07.007. Chinese.

PubMed [citation]

PMID:: 31302911

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005204635.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

Variant summary: TCTN1 c.342-8A>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Two predict the variant abolishes a 3' acceptor site. One predict the variant weakens a 3' acceptor site. Four predict the variant creates a 3' acceptor site. At least one publication reports experimental evidence that this variant affects mRNA splicing due to an insertion of 7 nucleotides from intron 2, resulting in a frameshift and premature termination codon (Wang_2019). The variant was absent in 162340 control chromosomes. c.342-8A>G has been reported in the literature in compound heterozygous individuals affected with Joubert Syndrome And Related Disorders (Wang_2019). These data indicate that the variant may be associated with disease. The following publication have been ascertained in the context of this evaluation (PMID: 31302911). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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