NM_004168.3(SDHA):c.1900A>G (p.Thr634Ala) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Jun 13, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000465027.2

Allele description [Variation Report for NM_004168.3(SDHA):c.1900A>G (p.Thr634Ala)]

NM_004168.3(SDHA):c.1900A>G (p.Thr634Ala)

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.1900A>G (p.Thr634Ala)
HGVS:
  • NC_000005.10:g.254498A>G
  • NG_012339.1:g.41258A>G
  • NM_004168.3:c.1900A>G
  • NP_004159.2:p.Thr634Ala
  • NC_000005.9:g.254613A>G
Protein change:
T634A
Links:
dbSNP: rs1017441235
NCBI 1000 Genomes Browser:
rs1017441235
Molecular consequence:
  • NM_004168.3:c.1900A>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

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000553905Invitaecriteria provided, single submitter
Uncertain significance
(Jun 13, 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, SCV000553905.3

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

Description

This sequence change replaces threonine with alanine at codon 634 of the SDHA protein (p.Thr634Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SDHA-related disease. ClinVar contains an entry for this variant (Variation ID: 412383). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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

Support Center