NM_020458.4(TTC7A):c.1018dup (p.Asp340fs) AND Multiple gastrointestinal atresias

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 2, 2022
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:: RCV001220533.7

Allele description [Variation Report for NM_020458.4(TTC7A):c.1018dup (p.Asp340fs)]

NM_020458.4(TTC7A):c.1018dup (p.Asp340fs)

Gene:

TTC7A:tetratricopeptide repeat domain 7A [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_020458.4(TTC7A):c.1018dup (p.Asp340fs)

HGVS:

NC_000002.12:g.46995152dup
NG_034143.2:g.84024dup
NM_001288951.2:c.1018dup
NM_001288953.2:c.916dup
NM_001288955.2:c.-45dup
NM_020458.4:c.1018dupMANE SELECT
NP_001275880.1:p.Asp340fs
NP_001275882.1:p.Asp306fs
NP_065191.2:p.Asp340fs
LRG_1323t1:c.1018dup
LRG_1323:g.84024dup
LRG_1323p1:p.Asp340fs
NC_000002.11:g.47222289_47222290insG
NC_000002.11:g.47222291dup
NG_034143.1:g.84024dup
NM_020458.3:c.1018dup

Protein change:

D306fs

Links:

dbSNP: rs762504554

NCBI 1000 Genomes Browser:

rs762504554

Molecular consequence:

NM_001288955.2:c.-45dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001288951.2:c.1018dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001288953.2:c.916dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_020458.4:c.1018dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Multiple gastrointestinal atresias
Synonyms:: FAMILIAL INTESTINAL POLYATRESIA SYNDROME; Multiple intestinal atresia
Identifiers:: MONDO: MONDO:0009465; MedGen: C0220744; Orphanet: 2300

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001392528	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 2, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23830146, 24292712, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001392528

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 2, 2022)

germline

clinical testing

PubMed (3)
[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

Whole-exome sequencing identifies tetratricopeptide repeat domain 7A (TTC7A) mutations for combined immunodeficiency with intestinal atresias.

Chen R, Giliani S, Lanzi G, Mias GI, Lonardi S, Dobbs K, Manis J, Im H, Gallagher JE, Phanstiel DH, Euskirchen G, Lacroute P, Bettinger K, Moratto D, Weinacht K, Montin D, Gallo E, Mangili G, Porta F, Notarangelo LD, Pedretti S, Al-Herz W, et al.

J Allergy Clin Immunol. 2013 Sep;132(3):656-664.e17. doi: 10.1016/j.jaci.2013.06.013. Epub 2013 Jul 4.

PubMed [citation]

PMID:: 23830146
PMCID:: PMC3759618

TTC7A mutations disrupt intestinal epithelial apicobasal polarity.

Bigorgne AE, Farin HF, Lemoine R, Mahlaoui N, Lambert N, Gil M, Schulz A, Philippet P, Schlesser P, Abrahamsen TG, Oymar K, Davies EG, Ellingsen CL, Leteurtre E, Moreau-Massart B, Berrebi D, Bole-Feysot C, Nischke P, Brousse N, Fischer A, Clevers H, de Saint Basile G.

J Clin Invest. 2014 Jan;124(1):328-37.

PubMed [citation]

PMID:: 24292712
PMCID:: PMC3871247

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001392528.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 949136). This variant has not been reported in the literature in individuals affected with TTC7A-related conditions. This variant is present in population databases (rs762504554, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Asp340Glyfs*45) in the TTC7A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TTC7A are known to be pathogenic (PMID: 23830146, 24292712).

#	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: Apr 7, 2025

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