NM_003172.4(SURF1):c.747C>A (p.Asn249Lys) AND Leigh syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 28, 2021
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:: RCV001928116.4

Allele description [Variation Report for NM_003172.4(SURF1):c.747C>A (p.Asn249Lys)]

NM_003172.4(SURF1):c.747C>A (p.Asn249Lys)

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.747C>A (p.Asn249Lys)

HGVS:

NC_000009.12:g.133352450G>T
NG_008477.1:g.9057C>A
NM_001280787.1:c.420C>A
NM_003172.4:c.747C>AMANE SELECT
NP_001267716.1:p.Asn140Lys
NP_003163.1:p.Asn249Lys
NC_000009.11:g.136219305G>T

Protein change:

N140K

Links:

dbSNP: rs1208965322

NCBI 1000 Genomes Browser:

rs1208965322

Molecular consequence:

NM_001280787.1:c.420C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003172.4:c.747C>A - 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

Recent activity

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Mus musculus 14, 17 days embryo head cDNA, RIKEN full-length enriched library, c...
Mus musculus 14, 17 days embryo head cDNA, RIKEN full-length enriched library, clone:3230401I01 product:GLUTAMYL TRNA SYNTHETASE homolog [Homo sapiens], full insert sequence
gi|26380219|dbj|AK014324.2|

Nucleotide
PREDICTED: Mus musculus centrosomal protein 57 (Cep57), transcript variant X4, m...
PREDICTED: Mus musculus centrosomal protein 57 (Cep57), transcript variant X4, misc_RNA
gi|1907200827|ref|XR_001779042.3|

Nucleotide
Z0419
Z0419

biosample
Homologene neighbors for GEO Profiles (Select 112467023) (0)
GEO Profiles
Homologene neighbors for GEO Profiles (Select 65011404) (0)
GEO Profiles

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002178083	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 28, 2021)	germline	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

SCV002178083

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 28, 2021)

germline

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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002178083.3

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with SURF1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 249 of the SURF1 protein (p.Asn249Lys).

#	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

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