NM_003172.4(SURF1):c.833+1_833+2insACCTGGGGAC AND Leigh syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 22, 2024
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:: RCV002010885.4

Allele description [Variation Report for NM_003172.4(SURF1):c.833+1_833+2insACCTGGGGAC]

NM_003172.4(SURF1):c.833+1_833+2insACCTGGGGAC

Gene:

SURF1:SURF1 cytochrome c oxidase assembly factor [Gene - OMIM - HGNC]

Variant type:

Insertion

Cytogenetic location:

9q34.2

Genomic location:

Preferred name:

NM_003172.4(SURF1):c.833+1_833+2insACCTGGGGAC

HGVS:

NC_000009.12:g.133352065_133352066insGTCCCCAGGT
NG_008477.1:g.9447_9448insGGACACCTGG
NM_001280787.1:c.506+1_506+2insACCTGGGGAC
NM_003172.4:c.833+1_833+2insACCTGGGGACMANE SELECT
NC_000009.11:g.136218914_136218915insCCAGGTGTCC
NC_000009.11:g.136218920_136218921insGTCCCCAGGT

Links:

dbSNP: rs2119079909

NCBI 1000 Genomes Browser:

rs2119079909

Molecular consequence:

NM_001280787.1:c.506+1_506+2insACCTGGGGAC - splice donor variant - [Sequence Ontology: SO:0001575]
NM_003172.4:c.833+1_833+2insACCTGGGGAC - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Leigh syndrome (NULS)
Synonyms:: Leigh Disease; Subacute necrotizing encephalopathy; Necrotizing encephalopathy infantile subacute of Leigh; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009723; MedGen: C0023264; Orphanet: 506; OMIM: 256000

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002290599	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 22, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 22488715, 29933018, 17576681, 9536098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002290599

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 22, 2024)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

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

SURF1-associated Leigh syndrome: a case series and novel mutations.

Lee IC, El-Hattab AW, Wang J, Li FY, Weng SW, Craigen WJ, Wong LJ.

Hum Mutat. 2012 Aug;33(8):1192-200. doi: 10.1002/humu.22095. Epub 2012 Apr 30.

PubMed [citation]

PMID:: 22488715

SURF1 mutations in Chinese patients with Leigh syndrome: Novel mutations, mutation spectrum, and the functional consequences.

Li Y, Wen S, Li D, Xie J, Wei X, Li X, Liu Y, Fang H, Yang Y, Lyu J.

Gene. 2018 Oct 20;674:15-24. doi: 10.1016/j.gene.2018.06.058. Epub 2018 Jun 19.

PubMed [citation]

PMID:: 29933018

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002290599.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change affects a splice site in intron 8 of the SURF1 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with Leigh syndrome (PMID: 22488715, 29933018). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1502070). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine