NM_000368.5(TSC1):c.1960C>G (p.Gln654Glu) AND not provided

Germline classification:: Benign/Likely benign (5 submissions)
Last evaluated:: Jul 1, 2022
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:: RCV000034604.22

Allele description [Variation Report for NM_000368.5(TSC1):c.1960C>G (p.Gln654Glu)]

NM_000368.5(TSC1):c.1960C>G (p.Gln654Glu)

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.1960C>G (p.Gln654Glu)

Other names:

p.GLN654Glu; p.Q654E:CAG>GAG

HGVS:

NC_000009.12:g.132905618G>C
NG_012386.1:g.44016C>G
NM_000368.5:c.1960C>GMANE SELECT
NM_001162426.2:c.1957C>G
NM_001162427.2:c.1807C>G
NM_001362177.2:c.1597C>G
NP_000359.1:p.Gln654Glu
NP_000359.1:p.Gln654Glu
NP_001155898.1:p.Gln653Glu
NP_001155899.1:p.Gln603Glu
NP_001349106.1:p.Gln533Glu
LRG_486t1:c.1960C>G
LRG_486:g.44016C>G
LRG_486p1:p.Gln654Glu
NC_000009.11:g.135781005G>C
NM_000368.3:c.1960C>G
NM_000368.4:c.1960C>G
NM_001162427.1:c.1807C>G
Q92574:p.Gln654Glu
p.(Gln654Glu)

Protein change:

Q533E

Links:

Tuberous sclerosis database (TSC1): TSC1_00282; UniProtKB: Q92574#VAR_009407; dbSNP: rs75820036

NCBI 1000 Genomes Browser:

rs75820036

Molecular consequence:

NM_000368.5:c.1960C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001162426.2:c.1957C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001162427.2:c.1807C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001362177.2:c.1597C>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000043512	Biesecker Lab/Clinical Genomics Section, National Institutes of Health - ClinSeq	no assertion criteria provided	probably not pathogenic (Jul 13, 2012)	germline	research	PubMed (1) [See all records that cite this PMID]
SCV000169088	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Benign (Nov 15, 2018)	germline	clinical testing	Citation Link,
SCV001146266	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Benign (Feb 4, 2019)	germline	clinical testing	PubMed (17) [See all records that cite these PMIDs] 22703879, 26332594, 25498131, 24789117, 22490766, 22558107, 14642745, 27600092, 29458892, 29740858, 10570911, 12015165, 14756965, 16554133, 16981987, 19254590, 26467025
SCV002774052	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Benign (Feb 4, 2019)	unknown	clinical testing	PubMed (25) [See all records that cite these PMIDs] 22703879, 26332594, 25498131, 24789117, 22490766, 22558107, 14642745, 23389244, 27600092, 9242607, 30794603, 32211034, 32917966, 31927531, 23514105, 29458892, 29740858, 10570911, 12015165, 14756965, 16554133, 16981987, 19254590, 21811971, 26467025
SCV004156643	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Likely benign (Jul 1, 2022)	germline	clinical testing	Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	no	1	not provided	not provided	572	not provided	research

Citations

PubMed

Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes.

Johnston JJ, Rubinstein WS, Facio FM, Ng D, Singh LN, Teer JK, Mullikin JC, Biesecker LG.

Am J Hum Genet. 2012 Jul 13;91(1):97-108. doi: 10.1016/j.ajhg.2012.05.021. Epub 2012 Jun 14.

PubMed [citation]

PMID:: 22703879
PMCID:: PMC3397257

Identification of Medically Actionable Secondary Findings in the 1000 Genomes.

Olfson E, Cottrell CE, Davidson NO, Gurnett CA, Heusel JW, Stitziel NO, Chen LS, Hartz S, Nagarajan R, Saccone NL, Bierut LJ.

PLoS One. 2015;10(9):e0135193. doi: 10.1371/journal.pone.0135193.

PubMed [citation]

PMID:: 26332594
PMCID:: PMC4558085

See all PubMed Citations (25)

Details of each submission

From Biesecker Lab/Clinical Genomics Section, National Institutes of Health - ClinSeq, SCV000043512.1

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

Description

The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See PubMed ID:22703879 for details.

Description

Converted during submission to Likely benign.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	572	not provided	discovery		1	not provided	not provided	not provided

From GeneDx, SCV000169088.12

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

Description

This variant is associated with the following publications: (PMID: 25498131, 22703879, 10570911, 26332594, 16981987, 16554133, 22490766, 29740858, 30794603, 32211034)

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

From Athena Diagnostics, SCV001146266.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (17)

#	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 Quest Diagnostics Nichols Institute San Juan Capistrano, SCV002774052.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (25)

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

From CeGaT Center for Human Genetics Tuebingen, SCV004156643.10

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

Description

TSC1: BP4, BS1

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

Last Updated: Nov 30, 2024

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