NM_003002.4(SDHD):c.479G>T (p.Ter160Leu) AND not specified

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 4, 2018
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000454533.13

Allele description [Variation Report for NM_003002.4(SDHD):c.479G>T (p.Ter160Leu)]

NM_003002.4(SDHD):c.479G>T (p.Ter160Leu)

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.479G>T (p.Ter160Leu)

Other names:

*164L; *160L; *121L

HGVS:

NC_000011.10:g.112094969G>T
NG_012337.3:g.13123G>T
NM_001276503.2:c.*76G>T
NM_001276504.2:c.362G>T
NM_001276506.2:c.*177G>T
NM_003002.4:c.479G>TMANE SELECT
NP_001263433.1:p.Ter121Leu
NP_002993.1:p.Ter160Leu
LRG_9t1:c.479G>T
LRG_9:g.13123G>T
LRG_9p1:p.Ter160Leu
NC_000011.9:g.111965693G>T
NM_003002.2:c.479G>T
NM_003002.3:c.479G>T
NR_077060.2:n.568G>T
p.X160LeuextX4

Note:

NCBI staff reviewed the sequence information reported in PubMed 24367056 Fig. 2B to determine the location of this allele on the current reference sequence.

Protein change:

TER164LEU

Links:

OMIM: 602690.0030; dbSNP: rs201372601

NCBI 1000 Genomes Browser:

rs201372601

Molecular consequence:

NM_001276503.2:c.*76G>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001276506.2:c.*177G>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NR_077060.2:n.568G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001276504.2:c.362G>T - stop lost - [Sequence Ontology: SO:0001578]
NM_003002.4:c.479G>T - stop lost - [Sequence Ontology: SO:0001578]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000540308	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Oct 20, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000918203	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Dec 4, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000540308

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Oct 20, 2016)

germline

clinical testing

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

SCV000918203

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Dec 4, 2018)

germline

clinical testing

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

Citation Link

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

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Mutations in SDHD lead to autosomal recessive encephalomyopathy and isolated mitochondrial complex II deficiency.

Jackson CB, Nuoffer JM, Hahn D, Prokisch H, Haberberger B, Gautschi M, Häberli A, Gallati S, Schaller A.

J Med Genet. 2014 Mar;51(3):170-5. doi: 10.1136/jmedgenet-2013-101932. Epub 2013 Dec 23.

PubMed [citation]

PMID:: 24367056

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000540308.1

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

Description

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Extension variant reported in 1 proband with autosomal recessive encephalomyopathy and MT complex II deficiency - proband carried E69K on other allele. Complementation of a patient cell line supported the pathogenicity of the SDHD variants.

#	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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000918203.1

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

Description

Variant summary: SDHD c.479G>T (p.X160LeuextX3) changes the termination codon and is predicted to lead to an extended protein with additional 3 amino acids added to the normal C-terminus. The variant allele was found at a frequency of 4.1e-06 in 242834 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.479G>T has been reported in the literature in one individual affected with mitochondrial complex II deficiency in compound heterozygous state (Jackson_2014). This report does not provide unequivocal conclusions about association of the variant with Hereditary Paraganglioma-Pheochromocytoma Syndrome. One publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about causality of the variant (Jackson_2014). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as 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: Apr 20, 2024

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