NM_020458.4(TTC7A):c.535C>G (p.Leu179Val) AND Multiple gastrointestinal atresias

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 16, 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:: RCV003642408.2

Allele description [Variation Report for NM_020458.4(TTC7A):c.535C>G (p.Leu179Val)]

NM_020458.4(TTC7A):c.535C>G (p.Leu179Val)

Genes:

LOC126806211:CDK7 strongly-dependent group 2 enhancer GRCh37_chr2:47201305-47202504 [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.535C>G (p.Leu179Val)

HGVS:

NC_000002.12:g.46974990C>G
NG_034143.2:g.63862C>G
NG_082535.1:g.925C>G
NM_001288951.2:c.535C>G
NM_001288953.2:c.433C>G
NM_001288955.2:c.-370C>G
NM_020458.4:c.535C>GMANE SELECT
NP_001275880.1:p.Leu179Val
NP_001275882.1:p.Leu145Val
NP_065191.2:p.Leu179Val
LRG_1323t1:c.535C>G
LRG_1323:g.63862C>G
LRG_1323p1:p.Leu179Val
NC_000002.11:g.47202129C>G

Protein change:

L145V

Molecular consequence:

NM_001288955.2:c.-370C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001288951.2:c.535C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001288953.2:c.433C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_020458.4:c.535C>G - 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
SCV004480596	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 16, 2023)	germline	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

SCV004480596

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 16, 2023)

germline

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

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

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004480596.1

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

Description

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. 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. This variant has not been reported in the literature in individuals affected with TTC7A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 179 of the TTC7A protein (p.Leu179Val).

#	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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