NM_003002.4(SDHD):c.284T>C (p.Leu95Pro) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 19, 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:: RCV002433463.2

Allele description [Variation Report for NM_003002.4(SDHD):c.284T>C (p.Leu95Pro)]

NM_003002.4(SDHD):c.284T>C (p.Leu95Pro)

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.284T>C (p.Leu95Pro)

HGVS:

NC_000011.10:g.112088981T>C
NG_012337.3:g.7135T>C
NG_033145.1:g.2818A>G
NM_001276503.2:c.169+1008T>C
NM_001276504.2:c.167T>C
NM_001276506.2:c.284T>C
NM_003002.4:c.284T>CMANE SELECT
NP_001263433.1:p.Leu56Pro
NP_001263435.1:p.Leu95Pro
NP_002993.1:p.Leu95Pro
LRG_9t1:c.284T>C
LRG_9:g.7135T>C
LRG_9p1:p.Leu95Pro
NC_000011.9:g.111959705T>C
NM_003002.1:c.284T>C
NM_003002.2:c.284T>C
NR_077060.2:n.319T>C

Protein change:

L56P

Links:

dbSNP: rs80338846

NCBI 1000 Genomes Browser:

rs80338846

Molecular consequence:

NM_001276503.2:c.169+1008T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001276504.2:c.167T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276506.2:c.284T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_003002.4:c.284T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_077060.2:n.319T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002749858	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Aug 19, 2022)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 11391798, 12218630, 21348866, 23586964, 25300370, 25758995, 29777207, 30050099, 31194241 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002749858

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Aug 19, 2022)

germline

clinical testing

PubMed (9)
[See all records that cite these PMIDs]

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

Nearly all hereditary paragangliomas in the Netherlands are caused by two founder mutations in the SDHD gene.

Taschner PE, Jansen JC, Baysal BE, Bosch A, Rosenberg EH, Bröcker-Vriends AH, van Der Mey AG, van Ommen GJ, Cornelisse CJ, Devilee P.

Genes Chromosomes Cancer. 2001 Jul;31(3):274-81.

PubMed [citation]

PMID:: 11391798

Clinical report on the L95P mutation in a Dutch family with paraganglioma.

Cremers CW, De Mönnink JP, Arts N, Joosten FB, Kremer H, Hoefsloot L.

Otol Neurotol. 2002 Sep;23(5):755-9.

PubMed [citation]

PMID:: 12218630

See all PubMed Citations (9)

Details of each submission

From Ambry Genetics, SCV002749858.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

The p.L95P pathogenic mutation (also known as c.284T>C), located in coding exon 3 of the SDHD gene, results from a T to C substitution at nucleotide position 284. The leucine at codon 95 is replaced by proline, an amino acid with similar properties. This alteration has been described as a Dutch founder mutation and has been identified in multiple patients and families with paragangliomas/pheochromocytomas, and was shown to segregate with disease in at least two families (Taschner PE et al. Genes Chromosomes Cancer, 2001 Jul;31:274-81; Cremers CW et al. Otol. Neurotol., 2002 Sep;23:755-9; Hensen EF et al. Clin. Genet., 2012 Mar;81:284-8; van Hulsteijn LT et al. Clin. Endocrinol. (Oxf), 2013 Dec;79:824-31; Bayley JP et al. BMC Med. Genet., 2014 Oct;15:111; Heesterman BL et al. Eur J Hum Genet, 2018 09;26:1339-1347; Richter S et al. Genet Med, 2019 03;21:705-717; Dreijerink KMA et al. J Clin Endocrinol Metab, 2019 11;104:5421-5426). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#	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: May 1, 2024

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