NM_003172.4(SURF1):c.409C>T (p.Arg137Trp) AND Leigh syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jul 9, 2022
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:: RCV001168010.5

Allele description [Variation Report for NM_003172.4(SURF1):c.409C>T (p.Arg137Trp)]

NM_003172.4(SURF1):c.409C>T (p.Arg137Trp)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

9q34.2

Genomic location:

Preferred name:

NM_003172.4(SURF1):c.409C>T (p.Arg137Trp)

Other names:

p.Arg137Trp

HGVS:

NC_000009.12:g.133353855G>A
NG_008477.1:g.7652C>T
NM_001280787.1:c.82C>T
NM_003172.4:c.409C>TMANE SELECT
NP_001267716.1:p.Arg28Trp
NP_003163.1:p.Arg137Trp
NC_000009.11:g.136220710G>A
NM_003172.2:c.409C>T
NM_003172.3:c.409C>T
p.R137W

Protein change:

R137W

Links:

dbSNP: rs373551988

NCBI 1000 Genomes Browser:

rs373551988

Molecular consequence:

NM_001280787.1:c.82C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003172.4:c.409C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001330563	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Apr 27, 2017)	germline	clinical testing	Citation Link,
SCV003213273	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 9, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29933018, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001330563

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Apr 27, 2017)

germline

clinical testing

Citation Link,

SCV003213273

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 9, 2022)

germline

clinical testing

PubMed (2)
[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 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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Illumina Laboratory Services, Illumina, SCV001330563.1

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

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

#	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

From Invitae, SCV003213273.1

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

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 137 of the SURF1 protein (p.Arg137Trp). This variant is present in population databases (rs373551988, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with SURF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 215233). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects SURF1 function (PMID: 29933018). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 19, 2024

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