NM_003002.4(SDHD):c.10C>T (p.Leu4Phe) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Aug 14, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001343479.1

Allele description [Variation Report for NM_003002.4(SDHD):c.10C>T (p.Leu4Phe)]

NM_003002.4(SDHD):c.10C>T (p.Leu4Phe)

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.10C>T (p.Leu4Phe)
HGVS:
  • NC_000011.10:g.112086917C>T
  • NG_012337.3:g.5071C>T
  • NG_033145.1:g.4882G>A
  • NM_001276503.2:c.10C>T
  • NM_001276504.2:c.10C>T
  • NM_001276506.2:c.10C>T
  • NM_003002.4:c.10C>TMANE SELECT
  • NP_001263432.1:p.Leu4Phe
  • NP_001263433.1:p.Leu4Phe
  • NP_001263435.1:p.Leu4Phe
  • NP_002993.1:p.Leu4Phe
  • LRG_9t1:c.10C>T
  • LRG_9:g.5071C>T
  • LRG_9p1:p.Leu4Phe
  • NC_000011.9:g.111957641C>T
  • NM_003002.2:c.10C>T
  • NR_077060.2:n.45C>T
Protein change:
L4F
Links:
dbSNP: rs1032016970
NCBI 1000 Genomes Browser:
rs1032016970
Molecular consequence:
  • NM_001276503.2:c.10C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276504.2:c.10C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276506.2:c.10C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003002.4:c.10C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_077060.2:n.45C>T - 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 1 (PGL1)
Synonyms:
PARAGANGLIOMA, CAROTID BODY; PARAGANGLIOMAS, FAMILIAL NONCHROMAFFIN, 1; PGL 1; See all synonyms [MedGen]
Identifiers:
MedGen: C1868633; Orphanet: 29072; OMIM: 168000
Name:
Cowden syndrome 3 (CWS3)
Identifiers:
MONDO: MONDO:0014045; MedGen: CN166604; Orphanet: 201

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001537465Invitaecriteria provided, single submitter
Uncertain significance
(Aug 14, 2020)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001537465.1

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

Description

This sequence change replaces leucine with phenylalanine at codon 4 of the SDHD protein (p.Leu4Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SDHD-related conditions. ClinVar contains an entry for this variant (Variation ID: 822168). 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) performed at Invitae indicates that this missense variant is not expected to disrupt SDHD protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Oct 7, 2021

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