NM_003002.4(SDHD):c.49C>T (p.Arg17Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 9, 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:: RCV002334687.9

Allele description [Variation Report for NM_003002.4(SDHD):c.49C>T (p.Arg17Ter)]

NM_003002.4(SDHD):c.49C>T (p.Arg17Ter)

Genes:

LOC126861339:BRD4-independent group 4 enhancer GRCh37_chr11:111957035-111958234 [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.49C>T (p.Arg17Ter)

HGVS:

NC_000011.10:g.112086956C>T
NG_012337.3:g.5110C>T
NG_033145.1:g.4843G>A
NM_001276503.2:c.49C>T
NM_001276504.2:c.49C>T
NM_001276506.2:c.49C>T
NM_003002.4:c.49C>TMANE SELECT
NP_001263432.1:p.Arg17Ter
NP_001263433.1:p.Arg17Ter
NP_001263435.1:p.Arg17Ter
NP_002993.1:p.Arg17Ter
LRG_9t1:c.49C>T
LRG_9:g.5110C>T
LRG_9p1:p.Arg17Ter
NC_000011.9:g.111957680C>T
NM_001276503.1:c.49C>T
NM_003002.2:c.49C>T
NR_077060.2:n.84C>T

Protein change:

R17*

Links:

dbSNP: rs1314133983

NCBI 1000 Genomes Browser:

rs1314133983

Molecular consequence:

NR_077060.2:n.84C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001276503.2:c.49C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276504.2:c.49C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276506.2:c.49C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_003002.4:c.49C>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002640483	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jul 9, 2021)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 18213727, 22025150, 30050099, 31212687, 33362715, 33397040 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002640483

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jul 9, 2021)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Malignant paraganglioma caused by a novel germline mutation of the succinate dehydrogenase D-gene--a case report.

Papaspyrou K, Rossmann H, Fottner C, Weber MM, Mann W, Lackner KJ, Helling K.

Head Neck. 2008 Jul;30(7):964-9. doi: 10.1002/hed.20746.

PubMed [citation]

PMID:: 18213727

Novel SDHD gene mutation (H102R) in a patient with metastatic cervical paraganglioma effectively treated by peptide receptor radionuclide therapy.

Poeppel TD, Yuece A, Boy C, Metz KA, Kaminsky E, Neumann HP, Rosenbaum SJ, Mann K, Moeller LC.

J Clin Oncol. 2011 Nov 20;29(33):e812-5. doi: 10.1200/JCO.2011.36.2269. Epub 2011 Oct 24. No abstract available.

PubMed [citation]

PMID:: 22025150

See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV002640483.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

The p.R17* pathogenic mutation (also known as c.49C>T), located in coding exon 1 of the SDHD gene, results from a C to T substitution at nucleotide position 49. This changes the amino acid from an arginine to a stop codon within coding exon 1. This mutation has been detected in multiple individuals with paraganglioma-pheochromocytoma (PGL-PCC) syndrome (Papaspyrou K et al. Head Neck, 2008 Jul;30:964-9; Poeppel TD et al. J Clin Oncol, 2011 Nov;29:e812-5; Richter S et al. Genet Med, 2019 03;21:705-717; Gieldon L et al. Cancers (Basel), 2019 Jun;11; Choi H et al. Endocrinol Metab (Seoul), 2020 12;35:858-872; Ma X et al. Front Endocrinol (Lausanne), 2020 Dec;11:574662). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 24, 2024

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