NM_020458.4(TTC7A):c.1072C>T (p.Arg358Ter) AND Multiple gastrointestinal atresias

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 28, 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:: RCV000815999.6

Allele description [Variation Report for NM_020458.4(TTC7A):c.1072C>T (p.Arg358Ter)]

NM_020458.4(TTC7A):c.1072C>T (p.Arg358Ter)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_020458.4(TTC7A):c.1072C>T (p.Arg358Ter)

HGVS:

NC_000002.12:g.47005928C>T
NG_034143.2:g.94800C>T
NM_001288951.1:c.1072C>T
NM_001288951.2:c.1072C>T
NM_001288953.2:c.970C>T
NM_001288955.2:c.10C>T
NM_020458.4:c.1072C>TMANE SELECT
NP_001275880.1:p.Arg358Ter
NP_001275882.1:p.Arg324Ter
NP_001275884.1:p.Arg4Ter
NP_065191.2:p.Arg358Ter
LRG_1323t1:c.1072C>T
LRG_1323:g.94800C>T
LRG_1323p1:p.Arg358Ter
NC_000002.11:g.47233067C>T
NG_034143.1:g.94800C>T
NM_020458.3:c.1072C>T

Protein change:

R324*

Links:

dbSNP: rs1297794582

NCBI 1000 Genomes Browser:

rs1297794582

Molecular consequence:

NM_001288951.2:c.1072C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001288953.2:c.970C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001288955.2:c.10C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_020458.4:c.1072C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000956484	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 28, 2023)	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

SCV000956484

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 28, 2023)

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, SCV000956484.5

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

Description

This sequence change creates a premature translational stop signal (p.Arg358*) 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). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with TTC7A-related conditions. ClinVar contains an entry for this variant (Variation ID: 659060). 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: May 16, 2025

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