NM_004168.3(SDHA):c.1787A>G (p.Asp596Gly) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: May 23, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000560589.2

Allele description [Variation Report for NM_004168.3(SDHA):c.1787A>G (p.Asp596Gly)]

NM_004168.3(SDHA):c.1787A>G (p.Asp596Gly)

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_004168.3(SDHA):c.1787A>G (p.Asp596Gly)
HGVS:
  • NC_000005.10:g.251461A>G
  • NG_012339.1:g.38221A>G
  • NM_001330758.1:c.1552-2932A>G
  • NM_004168.3:c.1787A>G
  • NP_004159.2:p.Asp596Gly
  • NC_000005.9:g.251576A>G
  • NM_004168.2:c.1787A>G
Protein change:
D596G
Links:
dbSNP: rs1126557
NCBI 1000 Genomes Browser:
rs1126557
Molecular consequence:
  • NM_001330758.1:c.1552-2932A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_004168.3:c.1787A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Mitochondrial complex II deficiency
Identifiers:
MedGen: C1855008; Orphanet: 3208; OMIM: 252011
Name:
Paragangliomas 5 (PGL5)
Identifiers:
MedGen: C3279992; Orphanet: 29072; OMIM: 614165

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000651409Invitaecriteria provided, single submitter
Uncertain significance
(May 23, 2018)
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.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000651409.2

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

Description

This sequence change replaces aspartic acid with glycine at codon 596 of the SDHA protein (p.Asp596Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is present in population databases (rs1126557, ExAC 0.02%). This variant has not been reported in the literature in individuals with SDHA-related disease. ClinVar contains an entry for this variant (Variation ID: 472358). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C35"). 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: Mar 30, 2019

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