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NM_004168.4(SDHA):c.1534C>T (p.Arg512Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Nov 1, 2021
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:
RCV000566844.6

Allele description [Variation Report for NM_004168.4(SDHA):c.1534C>T (p.Arg512Ter)]

NM_004168.4(SDHA):c.1534C>T (p.Arg512Ter)

Gene:
SDHA:succinate dehydrogenase complex flavoprotein subunit A [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5p15.33
Genomic location:
Preferred name:
NM_004168.4(SDHA):c.1534C>T (p.Arg512Ter)
Other names:
p.Arg512*
HGVS:
  • NC_000005.10:g.240459C>T
  • NG_012339.1:g.27219C>T
  • NM_001294332.2:c.1390C>T
  • NM_001330758.2:c.1534C>T
  • NM_004168.4:c.1534C>TMANE SELECT
  • NP_001281261.1:p.Arg464Ter
  • NP_001317687.1:p.Arg512Ter
  • NP_004159.2:p.Arg512Ter
  • LRG_315t1:c.1534C>T
  • LRG_315:g.27219C>T
  • LRG_315p1:p.Arg512Ter
  • NC_000005.9:g.240574C>T
  • NM_004168.2:c.1534C>T
  • NM_004168.3:c.1534C>T
Protein change:
R464*
Links:
dbSNP: rs748089700
NCBI 1000 Genomes Browser:
rs748089700
Molecular consequence:
  • NM_001294332.2:c.1390C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001330758.2:c.1534C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_004168.4:c.1534C>T - nonsense - [Sequence Ontology: SO:0001587]

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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000664526Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Oct 29, 2021) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link,

SCV002527721Sema4, Sema4
criteria provided, single submitter

(Sema4 Curation Guidelines)		Pathogenic
(Nov 1, 2021) 		germlinecuration

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Clinical Aspects of SDHA-Related Pheochromocytoma and Paraganglioma: A Nationwide Study.

van der Tuin K, Mensenkamp AR, Tops CMJ, Corssmit EPM, Dinjens WN, van de Horst-Schrivers ANA, Jansen JC, de Jong MM, Kunst HPM, Kusters B, Leter EM, Morreau H, van Nesselrooij BMP, Oldenburg RA, Spruijt L, Hes FJ, Timmers HJLM.

J Clin Endocrinol Metab. 2018 Feb 1;103(2):438-445. doi: 10.1210/jc.2017-01762. Erratum in: J Clin Endocrinol Metab. 2018 May 1;103(5):2077. doi: 10.1210/jc.2018-00533.

PubMed [citation]
PMID:
29177515

Clinical, Diagnostic, and Treatment Characteristics of SDHA-Related Metastatic Pheochromocytoma and Paraganglioma.

Jha A, de Luna K, Balili CA, Millo C, Paraiso CA, Ling A, Gonzales MK, Viana B, Alrezk R, Adams KT, Tena I, Chen A, Neuzil J, Raygada M, Kebebew E, Taieb D, O'Dorisio MS, O'Dorisio T, Civelek AC, Stratakis CA, Mercado-Asis L, Pacak K.

Front Oncol. 2019;9:53. doi: 10.3389/fonc.2019.00053.

PubMed [citation]
PMID:
30854332
PMCID:
PMC6395427
See all PubMed Citations (8)

Details of each submission

From Ambry Genetics, SCV000664526.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

The p.R512* pathogenic mutation (also known as c.1534C>T), located in coding exon 11 of the SDHA gene, results from a C to T substitution at nucleotide position 1534. This changes the amino acid from an arginine to a stop codon within coding exon 11. This mutation has been reported in both the germline and in the tumor of an individual with an extra-adrenal paraganglioma and in the germline of an individual with a testis paraganglioma (Papathomas TG et al. Mod. Pathol. 2015 Jun;28:807-21; van der Tuin K et al. J. Clin. Endocrinol. Metab. 2018 02;103(2):438-445). In another study, the mutation was carried by a 53-year-old female with metastatic retroperitoneal paraganglioma (Jha A et al. Front Oncol, 2019 Feb;9:53). This mutation has also been identified in several individuals with SDHA-deficient gastrointestinal stromal tumors (Wagner AJ et al. Mod Pathol, 2013 Feb;26:289-94; Jha A et al. Front Oncol, 2019 Feb;9:53). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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

From Sema4, Sema4, SCV002527721.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (5)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 8, 2024