NM_000368.5(TSC1):c.524T>C (p.Val175Ala) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 27, 2021
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:: RCV001023799.2

Allele description [Variation Report for NM_000368.5(TSC1):c.524T>C (p.Val175Ala)]

NM_000368.5(TSC1):c.524T>C (p.Val175Ala)

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.524T>C (p.Val175Ala)

HGVS:

NC_000009.12:g.132921958A>G
NG_012386.1:g.27676T>C
NM_000368.5:c.524T>CMANE SELECT
NM_001162426.2:c.524T>C
NM_001162427.2:c.371T>C
NM_001362177.2:c.161T>C
NP_000359.1:p.Val175Ala
NP_000359.1:p.Val175Ala
NP_001155898.1:p.Val175Ala
NP_001155899.1:p.Val124Ala
NP_001349106.1:p.Val54Ala
LRG_486t1:c.524T>C
LRG_486:g.27676T>C
LRG_486p1:p.Val175Ala
NC_000009.11:g.135797345A>G
NM_000368.4:c.524T>C

Protein change:

V124A

Links:

dbSNP: rs1415895533

NCBI 1000 Genomes Browser:

rs1415895533

Molecular consequence:

NM_000368.5:c.524T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001162426.2:c.524T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001162427.2:c.371T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001362177.2:c.161T>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001185720	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Uncertain significance (Oct 27, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001185720

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Uncertain significance
(Oct 27, 2021)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Mutation landscape of TSC1/TSC2 in Chinese patients with tuberous sclerosis complex.

Meng Y, Yu C, Chen M, Yu X, Sun M, Yan H, Zhao W, Yu S.

J Hum Genet. 2021 Mar;66(3):227-236. doi: 10.1038/s10038-020-00839-0. Epub 2020 Sep 11.

PubMed [citation]

PMID:: 32917966

Details of each submission

From Ambry Genetics, SCV001185720.3

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

Description

The p.V175A variant (also known as c.524T>C), located in coding exon 5 of the TSC1 gene, results from a T to C substitution at nucleotide position 524. The valine at codon 175 is replaced by alanine, an amino acid with similar properties. This alteration was identified in a Chinese individual diagnosed with tuberous sclerosis complex (Meng Y et al. J Hum Genet, 2021 Mar;66:227-236). This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

Last Updated: Feb 28, 2024

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