NM_003002.4(SDHD):c.342T>A (p.Tyr114Ter) AND not specified

Clinical significance:Pathogenic (Last evaluated: Oct 29, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001000118.2

Allele description [Variation Report for NM_003002.4(SDHD):c.342T>A (p.Tyr114Ter)]

NM_003002.4(SDHD):c.342T>A (p.Tyr114Ter)

Gene:
SDHD:succinate dehydrogenase complex subunit D [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q23.1
Genomic location:
Preferred name:
NM_003002.4(SDHD):c.342T>A (p.Tyr114Ter)
HGVS:
  • NC_000011.10:g.112094832T>A
  • NG_012337.3:g.12986T>A
  • NM_001276503.2:c.197T>A
  • NM_001276504.2:c.225T>A
  • NM_001276506.2:c.*40T>A
  • NM_003002.4:c.342T>AMANE SELECT
  • NP_001263432.1:p.Met66Lys
  • NP_001263433.1:p.Tyr75Ter
  • NP_002993.1:p.Tyr114Ter
  • LRG_9t1:c.342T>A
  • LRG_9:g.12986T>A
  • LRG_9p1:p.Tyr114Ter
  • NC_000011.9:g.111965556T>A
  • NM_003002.3:c.342T>A
  • NR_077060.2:n.431T>A
Protein change:
M66K
Links:
dbSNP: rs1050032491
NCBI 1000 Genomes Browser:
rs1050032491
Molecular consequence:
  • NM_001276506.2:c.*40T>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001276503.2:c.197T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_077060.2:n.431T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_001276504.2:c.225T>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_003002.4:c.342T>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001156553ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratoriescriteria provided, single submitter
Pathogenic
(Oct 29, 2018)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001156553.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The SDHD c.342T>A; p.Tyr114Ter variant is reported in the literature in multiple individuals affected with paragangliomas (Andrews 2018, Timmers 2008). This variant is reported as pathogenic by multiple laboratories in ClinVar (Variation ID: 438437), and is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant results in a premature termination codon in the last exon of the SDHD gene. While this may not lead to nonsense-mediated decay, it is expected to create a truncated protein missing the last 46 amino acids. Based on available information, the p.Tyr114Ter variant is considered to be pathogenic. References: Andrews KA et al. Tumour risks and genotype-phenotype correlations associated with germline variants in succinate dehydrogenase subunit genes SDHB, SDHC and SDHD. J Med Genet. 2018 Jun;55(6):384-394. Timmers HJ et al. Mutations associated with succinate dehydrogenase D-related malignant paragangliomas. Clin Endocrinol (Oxf). 2008 Apr;68(4):561-6.

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

Last Updated: Dec 2, 2021

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