ClinVar Miner

Submissions for variant NM_001079866.2(BCS1L):c.703G>A (p.Gly235Arg)

dbSNP: rs368486097
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255431 SCV000321416 likely pathogenic not provided 2018-07-06 criteria provided, single submitter clinical testing The G235R variant in the BCS1L gene has been reported previously with another variant on the opposite allele (in trans) in two sisters with hearing loss and pili torti (Falco et al., 2017). The G235R variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The G235R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret G235R as a likely pathogenic variant.
Counsyl RCV000670051 SCV000794862 uncertain significance GRACILE syndrome 2017-10-18 criteria provided, single submitter clinical testing
Baylor Genetics RCV001329215 SCV001520590 uncertain significance Mitochondrial complex III deficiency nuclear type 1 2020-07-28 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Invitae RCV000255431 SCV002229223 pathogenic not provided 2024-01-29 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 235 of the BCS1L protein (p.Gly235Arg). This variant is present in population databases (rs368486097, gnomAD 0.003%). This missense change has been observed in individual(s) with Björnstad syndrome (PMID: 28322498). 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: 265046). 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%. For these reasons, this variant has been classified as Pathogenic.

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