ClinVar Miner

Submissions for variant NM_001079866.2(BCS1L):c.134G>A (p.Arg45His)

gnomAD frequency: 0.00001  dbSNP: rs754414354
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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 RCV001243753 SCV001416934 pathogenic not provided 2023-12-11 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 45 of the BCS1L protein (p.Arg45His). This variant is present in population databases (rs754414354, gnomAD 0.004%). This missense change has been observed in individual(s) with Bjornstad syndrome (PMID: 28322498). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 554577). 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: 12910490, 20727375). 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.
Myriad Genetics, Inc. RCV001810474 SCV002060380 uncertain significance Pili torti-deafness syndrome; GRACILE syndrome; Mitochondrial complex III deficiency nuclear type 1 2021-11-10 criteria provided, single submitter clinical testing NM_004328.4(BCS1L):c.134G>A(R45H) is a missense variant classified as a variant of uncertain significance in the context of BCS1L-related disorders. R45H has been observed in cases with relevant disease (PMID: 28322498). Functional assessments of this variant are not available in the literature. R45H has been observed in population frequency databases (gnomAD: NFE 0.01%). In summary, there is insufficient evidence to classify NM_004328.4(BCS1L):c.134G>A(R45H) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening.
GeneDx RCV001243753 SCV002504356 likely pathogenic not provided 2022-03-10 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28322498)
Revvity Omics, Revvity RCV001243753 SCV003819585 likely pathogenic not provided 2022-06-03 criteria provided, single submitter clinical testing

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