NM_001082538.3(TCTN1):c.736A>T (p.Lys246Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 19, 2023
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:: RCV001940214.3

Allele description [Variation Report for NM_001082538.3(TCTN1):c.736A>T (p.Lys246Ter)]

NM_001082538.3(TCTN1):c.736A>T (p.Lys246Ter)

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.736A>T (p.Lys246Ter)

HGVS:

NC_000012.12:g.110634693A>T
NG_030381.1:g.25667A>T
NM_001082537.3:c.736A>T
NM_001082538.3:c.736A>TMANE SELECT
NM_001173975.3:c.568A>T
NM_001173976.2:c.556A>T
NM_001319680.2:c.736A>T
NM_001319681.2:c.202A>T
NM_024549.6:c.780+230A>T
NP_001076006.1:p.Lys246Ter
NP_001076007.1:p.Lys246Ter
NP_001167446.1:p.Lys190Ter
NP_001167447.1:p.Lys186Ter
NP_001306609.1:p.Lys246Ter
NP_001306610.1:p.Lys68Ter
NC_000012.11:g.111072498A>T
NR_135088.2:n.1146A>T

Protein change:

K186*

Links:

dbSNP: rs748215804

NCBI 1000 Genomes Browser:

rs748215804

Molecular consequence:

NM_024549.6:c.780+230A>T - intron variant - [Sequence Ontology: SO:0001627]
NR_135088.2:n.1146A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001082537.3:c.736A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001082538.3:c.736A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001173975.3:c.568A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001173976.2:c.556A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001319680.2:c.736A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001319681.2:c.202A>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Familial aplasia of the vermis
Synonyms:: CEREBELLOPARENCHYMAL DISORDER IV; Joubert syndrome; Cerebelloparenchymal disorder 4; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0018772; MedGen: C0431399; Orphanet: 475; OMIM: PS213300

Name:: Meckel-Gruber syndrome
Synonyms:: DYSENCEPHALIA SPLANCHNOCYSTICA; Gruber syndrome; Dysencephalia splachnocystica
Identifiers:: MONDO: MONDO:0018921; MedGen: C0265215; OMIM: PS249000

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002186216	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 19, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 21725307, 22693042, 27894351, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002186216

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 19, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

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

A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition.

Garcia-Gonzalo FR, Corbit KC, Sirerol-Piquer MS, Ramaswami G, Otto EA, Noriega TR, Seol AD, Robinson JF, Bennett CL, Josifova DJ, García-Verdugo JM, Katsanis N, Hildebrandt F, Reiter JF.

Nat Genet. 2011 Jul 3;43(8):776-84. doi: 10.1038/ng.891.

PubMed [citation]

PMID:: 21725307
PMCID:: PMC3145011

Molecular characterization of Joubert syndrome in Saudi Arabia.

Alazami AM, Alshammari MJ, Salih MA, Alzahrani F, Hijazi H, Seidahmed MZ, Abu Safieh L, Aldosary M, Khan AO, Alkuraya FS.

Hum Mutat. 2012 Oct;33(10):1423-8. doi: 10.1002/humu.22134. Epub 2012 Jul 11.

PubMed [citation]

PMID:: 22693042

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV002186216.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Lys246*) in the TCTN1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TCTN1 are known to be pathogenic (PMID: 21725307, 22693042, 27894351). This variant is present in population databases (rs748215804, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with TCTN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1410963). For these reasons, this variant has been classified as 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: Mar 5, 2024

ClinVar

Relating variation to medicine