NM_003172.4(SURF1):c.665C>G (p.Pro222Arg) AND Leigh syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 25, 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:: RCV002988543.2

Allele description [Variation Report for NM_003172.4(SURF1):c.665C>G (p.Pro222Arg)]

NM_003172.4(SURF1):c.665C>G (p.Pro222Arg)

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.665C>G (p.Pro222Arg)

HGVS:

NC_000009.12:g.133352532G>C
NG_008477.1:g.8975C>G
NG_008477.2:g.8955C>G
NM_001280787.1:c.338C>G
NM_003172.4:c.665C>GMANE SELECT
NP_001267716.1:p.Pro113Arg
NP_003163.1:p.Pro222Arg
NC_000009.11:g.136219387G>C

Protein change:

P113R

Molecular consequence:

NM_001280787.1:c.338C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_003172.4:c.665C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Leigh syndrome (LS)
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
SCV003290243	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 25, 2023)	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

SCV003290243

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 25, 2023)

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV003290243.2

#	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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SURF1 protein function. ClinVar contains an entry for this variant (Variation ID: 2078270). This variant has not been reported in the literature in individuals affected with SURF1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 222 of the SURF1 protein (p.Pro222Arg).

#	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: Feb 20, 2024

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