ClinVar Miner

Submissions for variant NM_003172.4(SURF1):c.745A>G (p.Asn249Asp)

gnomAD frequency: 0.00016  dbSNP: rs587669420
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001699229 SCV000252343 likely benign not provided 2021-03-12 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 32380162)
Invitae RCV000699472 SCV000828185 uncertain significance Leigh syndrome 2024-01-27 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 249 of the SURF1 protein (p.Asn249Asp). This variant is present in population databases (rs587669420, gnomAD 0.2%). This missense change has been observed in individual(s) with clinical features of SURF1-related conditions (PMID: 20843780, 32380162). ClinVar contains an entry for this variant (Variation ID: 215226). 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 with a negative predictive value of 80%. Experimental studies have shown that this missense change does not substantially affect SURF1 function (PMID: 32380162). 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.
Illumina Laboratory Services, Illumina RCV000699472 SCV001329882 uncertain significance Leigh syndrome 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Clinical Genetics, Academic Medical Center RCV001699229 SCV001921655 uncertain significance not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV001699229 SCV001926750 uncertain significance not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001699229 SCV001971007 uncertain significance not provided no assertion criteria provided clinical testing

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