NM_003001.5(SDHC):c.295T>C (p.Tyr99His) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 18, 2020
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:: RCV000482240.5

Allele description [Variation Report for NM_003001.5(SDHC):c.295T>C (p.Tyr99His)]

NM_003001.5(SDHC):c.295T>C (p.Tyr99His)

Gene:

SDHC:succinate dehydrogenase complex subunit C [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q23.3

Genomic location:

Preferred name:

NM_003001.5(SDHC):c.295T>C (p.Tyr99His)

HGVS:

NC_000001.11:g.161356730T>C
NG_012767.1:g.47355T>C
NM_001035511.3:c.242-5599T>C
NM_001035512.3:c.193T>C
NM_001035513.3:c.136T>C
NM_001278172.3:c.140-5599T>C
NM_001407115.1:c.415T>C
NM_001407116.1:c.238T>C
NM_001407117.1:c.232T>C
NM_001407118.1:c.187T>C
NM_001407119.1:c.184T>C
NM_001407120.1:c.184T>C
NM_001407121.1:c.185-5599T>C
NM_003001.5:c.295T>CMANE SELECT
NP_001030589.1:p.Tyr65His
NP_001030590.1:p.Tyr46His
NP_001394044.1:p.Tyr139His
NP_001394045.1:p.Tyr80His
NP_001394046.1:p.Tyr78His
NP_001394047.1:p.Tyr63His
NP_001394048.1:p.Tyr62His
NP_001394049.1:p.Tyr62His
NP_002992.1:p.Tyr99His
NP_002992.1:p.Tyr99His
LRG_317t1:c.295T>C
LRG_317:g.47355T>C
LRG_317p1:p.Tyr99His
NC_000001.10:g.161326520T>C
NM_003001.3:c.295T>C
NR_103459.3:n.347T>C

Protein change:

Y139H

Links:

dbSNP: rs760678574

NCBI 1000 Genomes Browser:

rs760678574

Molecular consequence:

NM_001035511.3:c.242-5599T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001278172.3:c.140-5599T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001407121.1:c.185-5599T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001035512.3:c.193T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001035513.3:c.136T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407115.1:c.415T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407116.1:c.238T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407117.1:c.232T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407118.1:c.187T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407119.1:c.184T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407120.1:c.184T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_003001.5:c.295T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_103459.3:n.347T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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conserved unknown protein [Ectocarpus siliculosus]
conserved unknown protein [Ectocarpus siliculosus]
gi|298706433|emb|CBJ29429.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000570669	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Jun 16, 2016)	germline	clinical testing	Citation Link,
SCV001134813	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Aug 18, 2020)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000570669

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Jun 16, 2016)

germline

clinical testing

Citation Link,

SCV001134813

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Aug 18, 2020)

unknown

clinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Details of each submission

From GeneDx, SCV000570669.4

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

Description

This variant is denoted SDHC c.295T>C at the cDNA level, p.Tyr99His (Y99H) at the protein level, and results in the change of a Tyrosine to a Histidine (TAT>CAT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. SDHC Tyr99His was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Tyrosine and Histidine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. SDHC Tyr99His occurs at a position that is not conserved and is located in the mitochondrial intermembrane domain (UniProt). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether SDHC Tyr99His is pathogenic or benign. We consider it to be a variant of uncertain significance.

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV001134813.2

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

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

Last Updated: Jul 15, 2024

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