ClinVar Miner

Submissions for variant NM_004589.4(SCO1):c.521C>T (p.Pro174Leu)

dbSNP: rs104894630
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001291618 SCV001480180 pathogenic not provided 2021-02-01 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000006555 SCV002813807 likely pathogenic Mitochondrial complex 4 deficiency, nuclear type 4 2021-10-18 criteria provided, single submitter clinical testing
Invitae RCV001291618 SCV003442593 pathogenic not provided 2023-12-12 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 174 of the SCO1 protein (p.Pro174Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of mitochondrial complex IV deficiency (PMID: 11013136). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 6178). 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 expected to disrupt SCO1 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects SCO1 function (PMID: 11118289, 16520371, 17182746, 23345593, 24403053, 29381136). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000006555 SCV000026738 pathogenic Mitochondrial complex 4 deficiency, nuclear type 4 2000-11-01 no assertion criteria provided literature only

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