NM_000548.5(TSC2):c.5321G>C (p.Ser1774Thr) AND Hereditary cancer-predisposing syndrome

Germline classification:: Benign (2 submissions)
Last evaluated:: Sep 10, 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:: RCV000163420.11

Allele description [Variation Report for NM_000548.5(TSC2):c.5321G>C (p.Ser1774Thr)]

NM_000548.5(TSC2):c.5321G>C (p.Ser1774Thr)

Gene:

TSC2:TSC complex subunit 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_000548.5(TSC2):c.5321G>C (p.Ser1774Thr)

HGVS:

NC_000016.10:g.2088507G>C
NG_005895.1:g.44202G>C
NG_008617.1:g.54714C>G
NM_000548.5:c.5321G>CMANE SELECT
NM_001077183.3:c.5120G>C
NM_001114382.3:c.5252G>C
NM_001318827.2:c.5012G>C
NM_001318829.2:c.4976G>C
NM_001318831.2:c.4589G>C
NM_001318832.2:c.5153G>C
NM_001363528.2:c.5123G>C
NM_001370404.1:c.5189G>C
NM_001370405.1:c.5180G>C
NM_021055.3:c.5192G>C
NP_000539.2:p.Ser1774Thr
NP_001070651.1:p.Ser1707Thr
NP_001107854.1:p.Ser1751Thr
NP_001305756.1:p.Ser1671Thr
NP_001305758.1:p.Ser1659Thr
NP_001305760.1:p.Ser1530Thr
NP_001305761.1:p.Ser1718Thr
NP_001350457.1:p.Ser1708Thr
NP_001357333.1:p.Ser1730Thr
NP_001357334.1:p.Ser1727Thr
NP_066399.2:p.Ser1731Thr
LRG_487t1:c.5321G>C
LRG_487:g.44202G>C
NC_000016.9:g.2138508G>C
NM_000548.3:c.5321G>C
NM_000548.4:c.5321G>C
P49815:p.Ser1774Thr
p.S1774T
p.(Ser1774Thr)

Protein change:

S1530T

Links:

Tuberous sclerosis database (TSC2): TSC2_00891; UniProtKB: P49815#VAR_057015; dbSNP: rs9209

NCBI 1000 Genomes Browser:

rs9209

Molecular consequence:

NM_000548.5:c.5321G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001077183.3:c.5120G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001114382.3:c.5252G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001318827.2:c.5012G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001318829.2:c.4976G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001318831.2:c.4589G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001318832.2:c.5153G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001363528.2:c.5123G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370404.1:c.5189G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370405.1:c.5180G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_021055.3:c.5192G>C - 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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CLIP1 CAP-Gly domain containing linker protein 1 [Homo sapiens]
CLIP1 CAP-Gly domain containing linker protein 1 [Homo sapiens]
Gene ID:6249

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000213963	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Benign (Apr 6, 2015)	germline	clinical testing	Citation Link,
SCV002534052	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Benign (Sep 10, 2020)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000213963

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Benign
(Apr 6, 2015)

germline

clinical testing

Citation Link,

SCV002534052

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Benign
(Sep 10, 2020)

germline

curation

Citation Link

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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

Details of each submission

From Ambry Genetics, SCV000213963.8

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

Description

This alteration is classified as 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, SCV002534052.1

#	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: Jun 9, 2024

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