NM_003002.4(SDHD):c.340T>G (p.Tyr114Asp) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 3, 2020
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:: RCV002451642.9

Allele description [Variation Report for NM_003002.4(SDHD):c.340T>G (p.Tyr114Asp)]

NM_003002.4(SDHD):c.340T>G (p.Tyr114Asp)

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.340T>G (p.Tyr114Asp)

HGVS:

NC_000011.10:g.112094830T>G
NG_012337.3:g.12984T>G
NM_001276503.2:c.195T>G
NM_001276504.2:c.223T>G
NM_001276506.2:c.*38T>G
NM_003002.4:c.340T>GMANE SELECT
NP_001263432.1:p.Thr65=
NP_001263433.1:p.Tyr75Asp
NP_002993.1:p.Tyr114Asp
LRG_9t1:c.340T>G
LRG_9:g.12984T>G
LRG_9p1:p.Tyr114Asp
NC_000011.9:g.111965554T>G
NM_003002.2:c.340T>G
NR_077060.2:n.429T>G

Protein change:

Y114D

Links:

dbSNP: rs876659276

NCBI 1000 Genomes Browser:

rs876659276

Molecular consequence:

NM_001276506.2:c.*38T>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001276504.2:c.223T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_003002.4:c.340T>G - missense variant - [Sequence Ontology: SO:0001583]
NR_077060.2:n.429T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001276503.2:c.195T>G - synonymous variant - [Sequence Ontology: SO:0001819]

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
SCV002614372	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Nov 3, 2020)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002614372

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Nov 3, 2020)

germline

clinical testing

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

Details of each submission

From Ambry Genetics, SCV002614372.2

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

Description

The p.Y114D pathogenic mutation (also known as c.340T>G), located in coding exon 4 of the SDHD gene, results from a T to G substitution at nucleotide position 340. The tyrosine at codon 114 is replaced by aspartic acid, an amino acid with highly dissimilar properties. Internal structural analysis shows that p.Y114D is on an interface, is part of a known functional motif, and is moderately destabilizing to the local structure (Ambry internal data). Two other alterations at the same codon, p.Y114N (c.340T>A) and p.Y114C (c.341A>G), have been detected in numerous individuals affected with paragangliomas and/or pheochromocytomas (Neumann H et al. JAMA. 2004 Aug 25;292(8):943-51; Liapis C et al. Anticancer Res. 2005 May-Jun;25(3c):2449-52; Benn D et al. J. Clin. Endocrinol. Metab. 2006 Mar;91(3):827-36; Antonello M et al. Eur. J. Vasc. Endovasc. Surg. 2008 Nov;36(5):517-9; Piccini V et al. Endocr. Relat. Cancer. 2012 Apr 10;19(2):149-55; Zdrojowy-Wena A and Bednarek-Tupikowska G. Neuro Endocrinol. Lett. 2014;35(5):355-8; Bennedbæk M et al. Hered. Cancer Clin. Pract. 2016 Jun;14:13; Schiavi F et al. J Clin Endocrinol. Merab 2012;97(4):637-41). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). 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: Oct 26, 2024

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