U.S. flag

An official website of the United States government

NM_003002.4(SDHD):c.242C>T (p.Pro81Leu) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 28, 2024
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:
RCV002228002.12

Allele description [Variation Report for NM_003002.4(SDHD):c.242C>T (p.Pro81Leu)]

NM_003002.4(SDHD):c.242C>T (p.Pro81Leu)

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.242C>T (p.Pro81Leu)
HGVS:
  • NC_000011.10:g.112088939C>T
  • NG_012337.3:g.7093C>T
  • NG_033145.1:g.2860G>A
  • NM_001276503.2:c.169+966C>T
  • NM_001276504.2:c.125C>T
  • NM_001276506.2:c.242C>T
  • NM_003002.4:c.242C>TMANE SELECT
  • NP_001263433.1:p.Pro42Leu
  • NP_001263435.1:p.Pro81Leu
  • NP_002993.1:p.Pro81Leu
  • LRG_9t1:c.242C>T
  • LRG_9:g.7093C>T
  • LRG_9p1:p.Pro81Leu
  • NC_000011.9:g.111959663C>T
  • NM_001276506.1:c.242C>T
  • NM_003002.1:c.242C>T
  • NM_003002.2:c.242C>T
  • NM_003002.3:c.242C>T
  • NR_077060.2:n.277C>T
  • O14521:p.Pro81Leu
  • p.P81L
Protein change:
P42L; PRO81LEU
Links:
UniProtKB: O14521#VAR_010038; OMIM: 602690.0003; dbSNP: rs80338844
NCBI 1000 Genomes Browser:
rs80338844
Molecular consequence:
  • NM_001276503.2:c.169+966C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001276504.2:c.125C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276506.2:c.242C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003002.4:c.242C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_077060.2:n.277C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Carney-Stratakis syndrome
Synonyms:
PARAGANGLIOMA AND GASTROINTESTINAL STROMAL TUMOR; Paraganglioma and gastric stromal sarcoma; Paraganglioma and GIST; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0011740; MedGen: C1847319; Orphanet: 97286; OMIM: 606864
Name:
Pheochromocytoma
Synonyms:
Chromaffinoma; Chromaffin paraganglioma; Chromaffin tumor; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008233; MedGen: C0031511; Orphanet: 29072; OMIM: 171300; Human Phenotype Ontology: HP:0002666
Name:
Paragangliomas with sensorineural hearing loss
Identifiers:
MedGen: C1868633
Name:
Cowden syndrome 3 (CWS3)
Identifiers:
MONDO: MONDO:0014045; MedGen: CN166604; Orphanet: 201

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000287817Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jan 28, 2024) 		germlineclinical testing

PubMed (11)
[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

Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma.

Baysal BE, Ferrell RE, Willett-Brozick JE, Lawrence EC, Myssiorek D, Bosch A, van der Mey A, Taschner PE, Rubinstein WS, Myers EN, Richard CW 3rd, Cornelisse CJ, Devilee P, Devlin B.

Science. 2000 Feb 4;287(5454):848-51.

PubMed [citation]
PMID:
10657297

Novel mutations in the SDHD gene in pedigrees with familial carotid body paraganglioma and sensorineural hearing loss.

Badenhop RF, Cherian S, Lord RS, Baysal BE, Taschner PE, Schofield PR.

Genes Chromosomes Cancer. 2001 Jul;31(3):255-63.

PubMed [citation]
PMID:
11391796
See all PubMed Citations (11)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000287817.11

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (11)

Description

This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 81 of the SDHD protein (p.Pro81Leu). This variant is present in population databases (rs80338844, gnomAD 0.006%). This missense change has been observed in individual(s) with head and neck paraganglioma (HNP) or pheochromocytoma (PMID: 10657297, 11391796, 11897817, 15479192, 19454582, 21348866, 21937622, 23433498, 24436918, 25494863). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 6896). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SDHD protein function. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Jan 13, 2025