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NM_000368.5(TSC1):c.1084C>T (p.Pro362Ser)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(2);Uncertain significance(2)

Review status:
criteria provided, conflicting interpretations
Submissions:
5 (Most recent: Sep 25, 2021)
Last evaluated:
Feb 3, 2021
Accession:
VCV000064817.8
Variation ID:
64817
Description:
single nucleotide variant
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NM_000368.5(TSC1):c.1084C>T (p.Pro362Ser)

Allele ID
75746
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
9q34.13
Genomic location
9: 132911059 (GRCh38) GRCh38 UCSC
9: 135786446 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
Q92574:p.Pro362Ser
NC_000009.11:g.135786446G>A
NM_000368.4:c.1084C>T NP_000359.1:p.Pro362Ser missense
... more HGVS
Protein change
P362S, P241S, P311S
Other names
-
Canonical SPDI
NC_000009.12:132911058:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00003
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD) 0.00001
Links
ClinGen: CA004402
UniProtKB: Q92574#VAR_070649
Tuberous sclerosis database (TSC1): TSC1_00500
dbSNP: rs397514864
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely benign 1 criteria provided, single submitter Jan 8, 2015 RCV000217275.1
Uncertain significance 1 criteria provided, single submitter Feb 26, 2020 RCV000642024.4
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Feb 3, 2021 RCV000725515.2
not provided 1 no assertion provided - RCV000055009.2
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
TSC1 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
2813 2857

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Nov 24, 2015)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000337442.4
Submitted: (Sep 19, 2018)
Evidence details
Other databases
http://www.egl-eurofins.com/emvc…
Likely benign
(Jan 08, 2015)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000273367.5
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (1)
Comment:
Intact protein function observed in appropriate functional assay(s);Other data supporting benign classification
Uncertain significance
(Feb 26, 2020)
criteria provided, single submitter
Method: clinical testing
Tuberous sclerosis 1
Allele origin: germline
Invitae
Accession: SCV000763677.4
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (2)
Comment:
This sequence change replaces proline with serine at codon 362 of the TSC1 protein (p.Pro362Ser). The proline residue is moderately conserved and there is a … (more)
Likely benign
(Feb 03, 2021)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000524636.4
Submitted: (Sep 25, 2021)
Evidence details
Comment:
In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 22161988)
not provided
(-)
no assertion provided
Method: curation
TSC
Allele origin: germline
Tuberous sclerosis database (TSC1)
Accession: SCV000083227.2
Submitted: (Aug 09, 2013)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Functional assessment of TSC1 missense variants identified in individuals with tuberous sclerosis complex. Hoogeveen-Westerveld M Human mutation 2012 PMID: 22161988
LOVD v.2.0: the next generation in gene variant databases. Fokkema IF Human mutation 2011 PMID: 21520333
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=TSC1 - - - -

Text-mined citations for rs397514864...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 27, 2021