NM_000368.5(TSC1):c.532G>A (p.Val178Ile) AND Hereditary cancer-predisposing syndrome

Germline classification:: Benign/Likely benign (2 submissions)
Last evaluated:: Nov 18, 2020
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:: RCV000164135.8

Allele description [Variation Report for NM_000368.5(TSC1):c.532G>A (p.Val178Ile)]

NM_000368.5(TSC1):c.532G>A (p.Val178Ile)

Gene:

TSC1:TSC complex subunit 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q34.13

Genomic location:

Preferred name:

NM_000368.5(TSC1):c.532G>A (p.Val178Ile)

HGVS:

NC_000009.12:g.132921950C>T
NG_012386.1:g.27684G>A
NM_000368.5:c.532G>AMANE SELECT
NM_001162426.2:c.532G>A
NM_001162427.2:c.379G>A
NM_001362177.2:c.169G>A
NP_000359.1:p.Val178Ile
NP_000359.1:p.Val178Ile
NP_001155898.1:p.Val178Ile
NP_001155899.1:p.Val127Ile
NP_001349106.1:p.Val57Ile
LRG_486t1:c.532G>A
LRG_486:g.27684G>A
LRG_486p1:p.Val178Ile
NC_000009.11:g.135797337C>T
NM_000368.3:c.532G>A
NM_000368.4:c.532G>A
p.V178I
p.(Val178Ile)

Protein change:

V127I

Links:

Tuberous sclerosis database (TSC1): TSC1_00025; dbSNP: rs118203395

NCBI 1000 Genomes Browser:

rs118203395

Molecular consequence:

NM_000368.5:c.532G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001162426.2:c.532G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001162427.2:c.379G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001362177.2:c.169G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Hereditary neoplastic syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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
SCV000214750	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Apr 27, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV002531466	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Benign (Nov 18, 2020)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000214750

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(Apr 27, 2018)

germline

clinical testing

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

Citation Link,

SCV002531466

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Benign
(Nov 18, 2020)

germline

curation

Citation Link

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, curation

Citations

PubMed

Mutations in the TSC1 gene account for a minority of patients with tuberous sclerosis.

Ali JB, Sepp T, Ward S, Green AJ, Yates JR.

J Med Genet. 1998 Dec;35(12):969-72.

PubMed [citation]

PMID:: 9863590
PMCID:: PMC1051505

Details of each submission

From Ambry Genetics, SCV000214750.7

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

Description

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#	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 Sema4, Sema4, SCV002531466.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided

#	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: Oct 25, 2025

ClinVar

Relating variation to medicine