NM_000368.5(TSC1):c.1001C>T (p.Ser334Leu) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely benign (2 submissions)
Last evaluated:: Dec 9, 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:: RCV000572872.5

Allele description [Variation Report for NM_000368.5(TSC1):c.1001C>T (p.Ser334Leu)]

NM_000368.5(TSC1):c.1001C>T (p.Ser334Leu)

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.1001C>T (p.Ser334Leu)

HGVS:

NC_000009.12:g.132911481G>A
NG_012386.1:g.38153C>T
NM_000368.5:c.1001C>TMANE SELECT
NM_001162426.2:c.1001C>T
NM_001162427.2:c.848C>T
NM_001362177.2:c.638C>T
NP_000359.1:p.Ser334Leu
NP_000359.1:p.Ser334Leu
NP_001155898.1:p.Ser334Leu
NP_001155899.1:p.Ser283Leu
NP_001349106.1:p.Ser213Leu
LRG_486t1:c.1001C>T
LRG_486:g.38153C>T
LRG_486p1:p.Ser334Leu
NC_000009.11:g.135786868G>A
NM_000368.3:c.1001C>T
NM_000368.4:c.1001C>T
p.(Ser334Leu)

Protein change:

S213L

Links:

Tuberous sclerosis database (TSC1): TSC1_00279; dbSNP: rs118203481

NCBI 1000 Genomes Browser:

rs118203481

Molecular consequence:

NM_000368.5:c.1001C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001162426.2:c.1001C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001162427.2:c.848C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001362177.2:c.638C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000675346	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Apr 5, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19747374, 21309039 Citation Link,
SCV002530870	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Likely benign (Dec 9, 2020)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000675346

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(Apr 5, 2018)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV002530870

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Likely benign
(Dec 9, 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

Identification of a region required for TSC1 stability by functional analysis of TSC1 missense mutations found in individuals with tuberous sclerosis complex.

Mozaffari M, Hoogeveen-Westerveld M, Kwiatkowski D, Sampson J, Ekong R, Povey S, den Dunnen JT, van den Ouweland A, Halley D, Nellist M.

BMC Med Genet. 2009 Sep 11;10:88. doi: 10.1186/1471-2350-10-88.

PubMed [citation]

PMID:: 19747374
PMCID:: PMC2753308

Functional assessment of variants in the TSC1 and TSC2 genes identified in individuals with Tuberous Sclerosis Complex.

Hoogeveen-Westerveld M, Wentink M, van den Heuvel D, Mozaffari M, Ekong R, Povey S, den Dunnen JT, Metcalfe K, Vallee S, Krueger S, Bergoffen J, Shashi V, Elmslie F, Kwiatkowski D, Sampson J, Vidales C, Dzarir J, Garcia-Planells J, Dies K, Maat-Kievit A, van den Ouweland A, Halley D, et al.

Hum Mutat. 2011 Apr;32(4):424-35. doi: 10.1002/humu.21451. Epub 2011 Mar 8.

PubMed [citation]

PMID:: 21309039

Details of each submission

From Ambry Genetics, SCV000675346.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

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, SCV002530870.1

#	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 20, 2024

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