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NM_000548.5(TSC2):c.1839G>C (p.Gln613His) AND Tuberous sclerosis 2

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 12, 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:
RCV000532879.6

Allele description [Variation Report for NM_000548.5(TSC2):c.1839G>C (p.Gln613His)]

NM_000548.5(TSC2):c.1839G>C (p.Gln613His)

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.1839G>C (p.Gln613His)
HGVS:
  • NC_000016.10:g.2070578G>C
  • NG_005895.1:g.26273G>C
  • NM_000548.5:c.1839G>CMANE SELECT
  • NM_001077183.3:c.1839G>C
  • NM_001114382.3:c.1839G>C
  • NM_001318827.2:c.1728G>C
  • NM_001318829.2:c.1692G>C
  • NM_001318831.2:c.1239G>C
  • NM_001318832.2:c.1872G>C
  • NM_001363528.2:c.1839G>C
  • NM_001370404.1:c.1839G>C
  • NM_001370405.1:c.1839G>C
  • NM_021055.3:c.1839G>C
  • NP_000539.2:p.Gln613His
  • NP_001070651.1:p.Gln613His
  • NP_001107854.1:p.Gln613His
  • NP_001305756.1:p.Gln576His
  • NP_001305758.1:p.Gln564His
  • NP_001305760.1:p.Gln413His
  • NP_001305761.1:p.Gln624His
  • NP_001350457.1:p.Gln613His
  • NP_001357333.1:p.Gln613His
  • NP_001357334.1:p.Gln613His
  • NP_066399.2:p.Gln613His
  • LRG_487t1:c.1839G>C
  • LRG_487:g.26273G>C
  • NC_000016.9:g.2120579G>C
  • NM_000548.3:c.1839G>C
Protein change:
Q413H
Links:
dbSNP: rs1555505208
NCBI 1000 Genomes Browser:
rs1555505208
Molecular consequence:
  • NM_000548.5:c.1839G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001077183.3:c.1839G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001114382.3:c.1839G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001318827.2:c.1728G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001318829.2:c.1692G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001318831.2:c.1239G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001318832.2:c.1872G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001363528.2:c.1839G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001370404.1:c.1839G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001370405.1:c.1839G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_021055.3:c.1839G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Tuberous sclerosis 2 (TSC2)
Identifiers:
MONDO: MONDO:0013199; MedGen: C1860707; Orphanet: 805; OMIM: 613254

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000644290Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(May 12, 2021) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]
PMID:
17576681
PMCID:
PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]
PMID:
9536098
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000644290.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has been observed in individual(s) with tuberous sclerosis complex (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 467902). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with histidine at codon 613 of the TSC2 protein (p.Gln613His). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and histidine. This variant also falls at the last nucleotide of exon 17, which is part of the consensus splice site for this exon.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 28, 2024