ClinVar Genomic variation as it relates to human health
NM_003172.4(SURF1):c.688C>T (p.Arg230Ter)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_003172.4(SURF1):c.688C>T (p.Arg230Ter)
Variation ID: 280010 Accession: VCV000280010.13
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 9q34.2 9: 133352509 (GRCh38) [ NCBI UCSC ] 9: 136219364 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Dec 6, 2016 Feb 28, 2024 Jan 11, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_003172.4:c.688C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003163.1:p.Arg230Ter nonsense NM_001280787.1:c.361C>T NP_001267716.1:p.Arg121Ter nonsense NC_000009.12:g.133352509G>A NC_000009.11:g.136219364G>A NG_008477.1:g.8998C>T - Protein change
- R230*, R121*
- Other names
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- Canonical SPDI
- NC_000009.12:133352508:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00007
Trans-Omics for Precision Medicine (TOPMed) 0.00007
The Genome Aggregation Database (gnomAD), exomes 0.00011
Exome Aggregation Consortium (ExAC) 0.00016
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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SURF1 | - | - |
GRCh38 GRCh38 GRCh37 |
633 | 727 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jan 26, 2022 | RCV000321649.8 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jan 11, 2024 | RCV000631405.5 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Apr 24, 2020)
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criteria provided, single submitter
Method: clinical testing
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Leigh syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001338432.1
First in ClinVar: Jun 18, 2020 Last updated: Jun 18, 2020 |
Comment:
Variant summary: SURF1 c.688C>T (p.Arg230X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: SURF1 c.688C>T (p.Arg230X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 0.00011 in 251462 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in SURF1 causing Leigh Syndrome (0.00011 vs 0.0018). c.688C>T has been reported in the literature in multiple individuals affected with Leigh Syndrome (eg. Coenen_1999, Pieutowska-Abramczuk_2009, Wedatilake_2013, Tay_2005). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Jan 26, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000329713.8
First in ClinVar: Dec 06, 2016 Last updated: Mar 04, 2023 |
Comment:
Reported previously in association with autosomal recessive Leigh syndrome due to COX deficiency (Coenen et al., 1999; Pecina et al., 2003; Wedatilake et al., 2013); … (more)
Reported previously in association with autosomal recessive Leigh syndrome due to COX deficiency (Coenen et al., 1999; Pecina et al., 2003; Wedatilake et al., 2013); Published functional studies demonstrate a damaging effect as this variant is associated with reduced COX complexes and accumulation of incomplete COX assemblies (Pecina et al., 2003); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 18583168, 25525159, 23829769, 16083427, 10558868, 12943968, 14557577, 10746561, 24462369) (less)
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Pathogenic
(Jan 25, 2019)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002018898.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Jan 11, 2024)
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criteria provided, single submitter
Method: clinical testing
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Leigh syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000752476.4
First in ClinVar: May 28, 2018 Last updated: Feb 28, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg230*) in the SURF1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg230*) in the SURF1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SURF1 are known to be pathogenic (PMID: 10443880, 22488715, 24027061). This variant is present in population databases (rs782623477, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with Leigh syndrome (PMID: 10558868, 10746561, 14557577, 24462369). It has also been observed to segregate with disease in related individuals. This variant is also known as c.702T>C. ClinVar contains an entry for this variant (Variation ID: 280010). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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A founder mutation in PET100 causes isolated complex IV deficiency in Lebanese individuals with Leigh syndrome. | Lim SC | American journal of human genetics | 2014 | PMID: 24462369 |
SURF1 deficiency causes demyelinating Charcot-Marie-Tooth disease. | Echaniz-Laguna A | Neurology | 2013 | PMID: 24027061 |
SURF1 deficiency: a multi-centre natural history study. | Wedatilake Y | Orphanet journal of rare diseases | 2013 | PMID: 23829769 |
SURF1-associated Leigh syndrome: a case series and novel mutations. | Lee IC | Human mutation | 2012 | PMID: 22488715 |
High prevalence of SURF1 c.845_846delCT mutation in Polish Leigh patients. | Piekutowska-Abramczuk D | European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society | 2009 | PMID: 18583168 |
Unusual clinical presentations in four cases of Leigh disease, cytochrome C oxidase deficiency, and SURF1 gene mutations. | Tay SK | Journal of child neurology | 2005 | PMID: 16225813 |
SURF1 gene mutations in three cases with Leigh syndrome and cytochrome c oxidase deficiency. | Moslemi AR | Neurology | 2003 | PMID: 14557577 |
Missense mutations in SURF1 associated with deficient cytochrome c oxidase assembly in Leigh syndrome patients. | Poyau A | Human genetics | 2000 | PMID: 10746561 |
SURFEIT-1 gene analysis and two-dimensional blue native gel electrophoresis in cytochrome c oxidase deficiency. | Coenen MJ | Biochemical and biophysical research communications | 1999 | PMID: 10558868 |
Loss-of-function mutations of SURF-1 are specifically associated with Leigh syndrome with cytochrome c oxidase deficiency. | Tiranti V | Annals of neurology | 1999 | PMID: 10443880 |
Text-mined citations for rs782623477 ...
HelpRecord last updated Mar 17, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.