NM_003002.4(SDHD):c.3G>C (p.Met1Ile) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 22, 2021
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:: RCV000492533.10

Allele description [Variation Report for NM_003002.4(SDHD):c.3G>C (p.Met1Ile)]

NM_003002.4(SDHD):c.3G>C (p.Met1Ile)

Genes:

LOC126861339:BRD4-independent group 4 enhancer GRCh37_chr11:111957035-111958234 [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.3G>C (p.Met1Ile)

Other names:

p.Met1?

HGVS:

NC_000011.10:g.112086910G>C
NG_012337.3:g.5064G>C
NG_033145.1:g.4889C>G
NM_001276503.2:c.3G>C
NM_001276504.2:c.3G>C
NM_001276506.2:c.3G>C
NM_003002.4:c.3G>CMANE SELECT
NP_001263432.1:p.Met1Ile
NP_001263433.1:p.Met1Ile
NP_001263435.1:p.Met1Ile
NP_002993.1:p.Met1Ile
LRG_9t1:c.3G>C
LRG_9:g.5064G>C
LRG_9p1:p.Met1Ile
NC_000011.9:g.111957634G>C
NM_003002.1:c.3G>C
NM_003002.2:c.3G>C
NM_003002.3:c.3G>C
NR_077060.2:n.38G>C

Protein change:

M1I; MET1ILE

Links:

OMIM: 602690.0015; dbSNP: rs80338842

NCBI 1000 Genomes Browser:

rs80338842

Molecular consequence:

NM_001276503.2:c.3G>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001276504.2:c.3G>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001276506.2:c.3G>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_003002.4:c.3G>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001276503.2:c.3G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276504.2:c.3G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276506.2:c.3G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_003002.4:c.3G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_077060.2:n.38G>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
SCV000581230	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jul 22, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12782822, 17406045 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000581230

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jul 22, 2021)

germline

clinical testing

PubMed (2)
[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

Hereditary paraganglioma due to the SDHD M1I mutation in a second Chinese family: a founder effect?

Lee SC, Chionh SB, Chong SM, Taschner PE.

Laryngoscope. 2003 Jun;113(6):1055-8.

PubMed [citation]

PMID:: 12782822

A Chinese family with familial paraganglioma syndrome due to succinate dehydrogenase deficiency.

Ma RC, Lam CW, Chan WB, So WY, Tong SF, Chow CC, Cockram CS.

Hong Kong Med J. 2007 Apr;13(2):151-4.

PubMed [citation]

PMID:: 17406045

Details of each submission

From Ambry Genetics, SCV000581230.7

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

Description

The p.M1? pathogenic mutation (also known as c.3G>C) is located in coding exon 1 of the SDHD gene and results from a G to C substitution at nucleotide position 1. This alters the methionine residue at the initiation codon. This mutation has been reported in multiple Asian families affected with early onset paragangliomas, and haplotype analysis has identified it as a Chinese founder mutation (Badenhop RF et al. Genes Chromosomes Cancer. 2001 Jul;31(3):255-63; Lee SC et al. Laryngoscope, 2003 Jun;113:1055-8; Ma RC et al. Hong Kong Med J, 2007 Apr;13:151-4; Zha Y et al. Laryngoscope. 2011 Aug;121(8); Wang CP et al. Oral Oncol. 2012 Feb;48(2):125-9; Ting KR et al. Hered Cancer Clin Pract 2020 Dec;18(1):24). This alteration is also denoted as p.M1I throughout the literature. In addition to the clinical data presented in the literature, since sequence variations that modify the initiation codon (ATG) are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame, 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: Nov 24, 2024

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