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NM_003002.4(SDHD):c.320T>G (p.Leu107Arg) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 3, 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:
RCV002229212.12

Allele description [Variation Report for NM_003002.4(SDHD):c.320T>G (p.Leu107Arg)]

NM_003002.4(SDHD):c.320T>G (p.Leu107Arg)

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.320T>G (p.Leu107Arg)
HGVS:
  • NC_000011.10:g.112094810T>G
  • NG_012337.3:g.12964T>G
  • NM_001276503.2:c.175T>G
  • NM_001276504.2:c.203T>G
  • NM_001276506.2:c.*18T>G
  • NM_003002.4:c.320T>GMANE SELECT
  • NP_001263432.1:p.Leu59Val
  • NP_001263433.1:p.Leu68Arg
  • NP_002993.1:p.Leu107Arg
  • LRG_9t1:c.320T>G
  • LRG_9:g.12964T>G
  • LRG_9p1:p.Leu107Arg
  • NC_000011.9:g.111965534T>G
  • NM_003002.2:c.320T>G
  • NM_003002.3:c.320T>G
  • NR_077060.2:n.409T>G
Protein change:
L107R
Links:
dbSNP: rs876658477
NCBI 1000 Genomes Browser:
rs876658477
Molecular consequence:
  • NM_001276506.2:c.*18T>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001276503.2:c.175T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276504.2:c.203T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003002.4:c.320T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_077060.2:n.409T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Carney-Stratakis syndrome
Synonyms:
Paraganglioma and gastric stromal sarcoma; Paraganglioma and gastrointestinal stromal tumor; 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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000554059Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Sep 3, 2023) 		germlineclinical testing

PubMed (4)
[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

Cardiac paraganglioma with a novel germline mutation of succinate dehydrogenase gene D.

Otani N, Sugano K, Inami S, Amano H, Arikawa T, Saito S, Imai K, Ushiama M, Yoshida T, Kimura N, Toyoda S, Inoue T.

Jpn J Clin Oncol. 2017 Dec 1;47(12):1193-1197. doi: 10.1093/jjco/hyx132.

PubMed [citation]
PMID:
28977582

Tumor-specific prognosis of mutation-positive patients with head and neck paragangliomas.

Sen I, Young WF Jr, Kasperbauer JL, Polonis K, Harmsen WS, Colglazier JJ, DeMartino RR, Oderich GS, Kalra M, Bower TC.

J Vasc Surg. 2020 May;71(5):1602-1612.e2. doi: 10.1016/j.jvs.2019.08.232. Epub 2020 Feb 5.

PubMed [citation]
PMID:
32035780
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000554059.9

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Leu107 amino acid residue in SDHD. Other variant(s) that disrupt this residue have been observed in individuals with SDHD-related conditions (PMID: 28977582), which suggests that this may be a clinically significant amino acid residue. 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. ClinVar contains an entry for this variant (Variation ID: 230274). This missense change has been observed in individuals with head and neck paragangliomas (PMID: 32035780, 34906457; Invitae). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 107 of the SDHD protein (p.Leu107Arg).

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

Last Updated: Oct 26, 2024