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NM_000368.5(TSC1):c.1029+3A>G AND Hereditary cancer-predisposing syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jul 21, 2023
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:
RCV003303090.3

Allele description [Variation Report for NM_000368.5(TSC1):c.1029+3A>G]

NM_000368.5(TSC1):c.1029+3A>G

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.1029+3A>G
HGVS:
  • NC_000009.12:g.132911450T>C
  • NG_012386.1:g.38184A>G
  • NM_000368.5:c.1029+3A>GMANE SELECT
  • NM_001162426.2:c.1029+3A>G
  • NM_001162427.2:c.876+3A>G
  • NM_001362177.2:c.666+3A>G
  • LRG_486t1:c.1029+3A>G
  • LRG_486:g.38184A>G
  • NC_000009.11:g.135786837T>C
  • NC_000009.11:g.135786837T>C
  • NM_000368.4:c.1029+3A>G
Links:
dbSNP: rs1554817334
NCBI 1000 Genomes Browser:
rs1554817334
Molecular consequence:
  • NM_000368.5:c.1029+3A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001162426.2:c.1029+3A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001162427.2:c.876+3A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001362177.2:c.666+3A>G - intron variant - [Sequence Ontology: SO:0001627]

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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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004000985Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Jul 21, 2023) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

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Summary from all submissions

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

Citations

PubMed

Initial experience from a renal genetics clinic demonstrates a distinct role in patient management.

Thomas CP, Freese ME, Ounda A, Jetton JG, Holida M, Noureddine L, Smith RJ.

Genet Med. 2020 Jun;22(6):1025-1035. doi: 10.1038/s41436-020-0772-y. Epub 2020 Mar 17. Erratum in: Genet Med. 2021 Oct;23(10):2017-2019. doi: 10.1038/s41436-020-01000-0.

PubMed [citation]
PMID:
32203225
PMCID:
PMC7272321

Details of each submission

From Ambry Genetics, SCV004000985.3

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

Description

The c.1029+3A>G intronic variant results from an A to G substitution 3 nucleotides after coding exon 8 in the TSC1 gene. One study reports that this alteration was identified in an individual diagnosed with Tuberous sclerosis complex (Thomas CP et al. Genet Med, 2020 Jun;22:1025-1035). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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

Last Updated: Sep 29, 2024