NM_020458.4(TTC7A):c.1189G>A (p.Val397Ile) AND Multiple gastrointestinal atresias

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 18, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000694371.8

Allele description [Variation Report for NM_020458.4(TTC7A):c.1189G>A (p.Val397Ile)]

NM_020458.4(TTC7A):c.1189G>A (p.Val397Ile)

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.1189G>A (p.Val397Ile)

HGVS:

NC_000002.12:g.47006045G>A
NG_034143.2:g.94917G>A
NM_001288951.2:c.1189G>A
NM_001288953.2:c.1087G>A
NM_001288955.2:c.127G>A
NM_020458.4:c.1189G>AMANE SELECT
NP_001275880.1:p.Val397Ile
NP_001275882.1:p.Val363Ile
NP_001275884.1:p.Val43Ile
NP_065191.2:p.Val397Ile
LRG_1323t1:c.1189G>A
LRG_1323:g.94917G>A
LRG_1323p1:p.Val397Ile
NC_000002.11:g.47233184G>A
NG_034143.1:g.94917G>A
NM_020458.2:c.1189G>A
NM_020458.3:c.1189G>A
p.Val397Ile

Protein change:

V363I

Links:

dbSNP: rs146284515

NCBI 1000 Genomes Browser:

rs146284515

Molecular consequence:

NM_001288951.2:c.1189G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001288953.2:c.1087G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001288955.2:c.127G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_020458.4:c.1189G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000822813	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 18, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001520480	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 21, 2019)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000822813

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 18, 2024)

germline

clinical testing

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

SCV001520480

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jun 21, 2019)

unknown

clinical testing

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

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
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000822813.6

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

Description

This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 397 of the TTC7A protein (p.Val397Ile). This variant is present in population databases (rs146284515, gnomAD 0.1%). 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: 572873). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TTC7A protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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

From Baylor Genetics, SCV001520480.1

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

Description

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].

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

Last Updated: Oct 8, 2024

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