ClinVar Miner

Submissions for variant NM_001079866.2(BCS1L):c.133C>T (p.Arg45Cys)

dbSNP: rs121908575
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001851700 SCV002240635 pathogenic not provided 2024-01-25 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 45 of the BCS1L protein (p.Arg45Cys). This variant is present in population databases (rs121908575, gnomAD 0.004%). This missense change has been observed in individual(s) with mitochondrial complex III deficiency (PMID: 12910490). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 6168). 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 BCS1L protein function with a positive predictive value of 95%. This variant disrupts the p.Arg45 amino acid residue in BCS1L. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 28322498). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV003472988 SCV004210798 likely pathogenic Pili torti-deafness syndrome 2024-03-18 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005025015 SCV005650488 likely pathogenic Pili torti-deafness syndrome; GRACILE syndrome; Mitochondrial complex III deficiency nuclear type 1 2024-04-02 criteria provided, single submitter clinical testing
OMIM RCV000006543 SCV000026726 pathogenic Mitochondrial complex III deficiency nuclear type 1 2009-06-01 no assertion criteria provided literature only

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