NM_003172.4(SURF1):c.1A>T (p.Met1Leu) AND Leigh syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 8, 2023
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:: RCV003620271.1

Allele description [Variation Report for NM_003172.4(SURF1):c.1A>T (p.Met1Leu)]

NM_003172.4(SURF1):c.1A>T (p.Met1Leu)

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.1A>T (p.Met1Leu)

HGVS:

NC_000009.12:g.133356453T>A
NG_008477.1:g.5033A>T
NG_008477.2:g.5034A>T
NG_182345.1:g.265T>A
NM_001280787.1:c.-275A>T
NM_003172.4:c.1A>TMANE SELECT
NP_003163.1:p.Met1Leu
NC_000009.11:g.136223329T>A

Protein change:

M1L

Molecular consequence:

NM_001280787.1:c.-275A>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_003172.4:c.1A>T - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_003172.4:c.1A>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
SCV004533770	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 8, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 19780766, 22488715, 29933018, 32445240, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004533770

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 8, 2023)

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 missense mutations promote a mild Leigh phenotype.

Piekutowska-Abramczuk D, Magner M, Popowska E, Pronicki M, Karczmarewicz E, Sykut-Cegielska J, Kmiec T, Jurkiewicz E, Szymanska-Debinska T, Bielecka L, Krajewska-Walasek M, Vesela K, Zeman J, Pronicka E.

Clin Genet. 2009 Aug;76(2):195-204. doi: 10.1111/j.1399-0004.2009.01195.x.

PubMed [citation]

PMID:: 19780766

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

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV004533770.1

#	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 the initiator methionine of the SURF1 mRNA. The next in-frame methionine is located at codon 110. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SURF1-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant disrupts a region of the SURF1 protein in which other variant(s) (p.Leu90Pro) have been determined to be pathogenic (PMID: 19780766, 22488715, 29933018, 32445240). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as 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: May 19, 2024

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