NM_003172.4(SURF1):c.563A>G (p.Asn188Ser) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 25, 2022
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:: RCV002222439.1

Allele description [Variation Report for NM_003172.4(SURF1):c.563A>G (p.Asn188Ser)]

NM_003172.4(SURF1):c.563A>G (p.Asn188Ser)

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.563A>G (p.Asn188Ser)

HGVS:

NC_000009.12:g.133352719T>C
NG_008477.1:g.8788A>G
NM_001280787.1:c.236A>G
NM_003172.4:c.563A>GMANE SELECT
NP_001267716.1:p.Asn79Ser
NP_003163.1:p.Asn188Ser
NC_000009.11:g.136219574T>C
NM_003172.2:c.563A>G
NM_003172.3:c.563A>G
p.N188S

Protein change:

N188S

Links:

dbSNP: rs200702528

NCBI 1000 Genomes Browser:

rs200702528

Molecular consequence:

NM_001280787.1:c.236A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_003172.4:c.563A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002500642	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Mar 25, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29933018, 26944241 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002500642

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Mar 25, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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

Outcome of Whole Exome Sequencing for Diagnostic Odyssey Cases of an Individualized Medicine Clinic: The Mayo Clinic Experience.

Lazaridis KN, Schahl KA, Cousin MA, Babovic-Vuksanovic D, Riegert-Johnson DL, Gavrilova RH, McAllister TM, Lindor NM, Abraham RS, Ackerman MJ, Pichurin PN, Deyle DR, Gavrilov DK, Hand JL, Klee EW, Stephens MC, Wick MJ, Atkinson EJ, Linden DR, Ferber MJ, Wieben ED, Farrugia G; et al.

Mayo Clin Proc. 2016 Mar;91(3):297-307. doi: 10.1016/j.mayocp.2015.12.018.

PubMed [citation]

PMID:: 26944241

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002500642.1

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

Description

Variant summary: SURF1 c.563A>G (p.Asn188Ser) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00012 in 249650 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in SURF1 causing Leigh Syndrome (0.00012 vs 0.0018), allowing no conclusion about variant significance. c.563A>G has been reported in the literature in a heterozygous individual affected with a suspected genetic disease (specific phenotype not provided) (Lazaridis_2016). This report does not provide unequivocal conclusions about association of the variant with Leigh Syndrome. Experimental evidence evaluating an impact on protein function showed that the variant decreases complex IV assembly without affecting SURF1 stability (Li_2018). This report does not allow convincing conclusions about the variant effect. A ClinVar submitter (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as 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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