NM_004168.4(SDHA):c.994C>T (p.Pro332Ser) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 6, 2022
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:: RCV000549735.9

Allele description [Variation Report for NM_004168.4(SDHA):c.994C>T (p.Pro332Ser)]

NM_004168.4(SDHA):c.994C>T (p.Pro332Ser)

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_004168.4(SDHA):c.994C>T (p.Pro332Ser)

Other names:

p.Pro332Ser

HGVS:

NC_000005.10:g.233575C>T
NG_012339.1:g.20335C>T
NM_001294332.2:c.850C>T
NM_001330758.2:c.994C>T
NM_004168.4:c.994C>TMANE SELECT
NP_001281261.1:p.Pro284Ser
NP_001317687.1:p.Pro332Ser
NP_004159.2:p.Pro332Ser
LRG_315t1:c.994C>T
LRG_315:g.20335C>T
LRG_315p1:p.Pro332Ser
NC_000005.9:g.233690C>T
NM_004168.2:c.994C>T
NM_004168.3:c.994C>T

Protein change:

P284S

Links:

dbSNP: rs373509391

NCBI 1000 Genomes Browser:

rs373509391

Molecular consequence:

NM_001294332.2:c.850C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330758.2:c.994C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004168.4:c.994C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Mitochondrial complex II deficiency, nuclear type 1
Synonyms:: Mitochondrial complex II deficiency; Complex 2 mitochondrial respiratory chain deficiency; Succinate CoQ reductase deficiency
Identifiers:: MONDO: MONDO:0100294; MedGen: C5700310; Orphanet: 3208; OMIM: 252011

Name:: Paragangliomas 5 (PPGL5)
Synonyms:: PHEOCHROMOCYTOMA/PARAGANGLIOMA SYNDROME 5
Identifiers:: MONDO: MONDO:0013602; MedGen: C3279992; Orphanet: 29072; OMIM: 614165

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000651477	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 6, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31666924, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000651477

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 6, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutational profile and genotype/phenotype correlation of non-familial pheochromocytoma and paraganglioma.

Albattal S, Alswailem M, Moria Y, Al-Hindi H, Dasouki M, Abouelhoda M, Alkhail HA, Alsuhaibani E, Alzahrani AS.

Oncotarget. 2019 Oct 15;10(57):5919-5931. doi: 10.18632/oncotarget.27194.

PubMed [citation]

PMID:: 31666924
PMCID:: PMC6800268

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000651477.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 332 of the SDHA protein (p.Pro332Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with paraganglioma (PMID: 31666924). ClinVar contains an entry for this variant (Variation ID: 472424). 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 disruptive. 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 24, 2024

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