ClinVar Miner

Submissions for variant NM_001257342.2(BCS1L):c.232A>G (p.Ser78Gly) (rs28937590)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Courtagen Diagnostics Laboratory,Courtagen Life Sciences RCV000006542 SCV000236535 pathogenic GRACILE syndrome 2014-09-26 criteria provided, single submitter clinical testing
GeneDx RCV000519547 SCV000617082 pathogenic not provided 2017-09-20 criteria provided, single submitter clinical testing The S78G pathogenic variant in the BCS1L gene has been reported previously in the homozygous state in multiple individuals of Finnish descent with features suggestive of GRACILE syndrome (Visapaa et al., 2002; Fellman et al., 2008). The S78G has also been reported in combination with a missense variant in an individual with hypotonia and complex III deficiency in addition to features of GRACILE syndrome (Visapaa et al., 2002). The S78G variant is observed in 26/6,614 (0.39%) alleles from individuals of Finnish background in the ExAC dataset (Lek et al., 2016). The S78G 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. This substitution occurs at a position that is conserved across species. Functional studies demonstrate that S78G is associated with decreased stability of the BCS1L protein (Visapaa et al., 2002). Transgenic mice with homozygosity for the S78G variant demonstrate decreased BCS1L expression and decreased Rieske iron-sulfur protein incorporation into complex III (Davoudi et al., 2014). We interpret S78G as a pathogenic variant.
Institute of Human Genetics,Klinikum rechts der Isar RCV000006542 SCV000680154 pathogenic GRACILE syndrome 2017-09-08 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000006542 SCV000698304 pathogenic GRACILE syndrome 2016-07-14 criteria provided, single submitter clinical testing Variant summary: The BCS1L c.232A>G (p.Ser78Gly) variant involves the alteration of a conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 48/122498 control chromosomes at a frequency of 0.0003918, which does not exceed the estimated maximal expected allele frequency of a pathogenic BCS1L variant (0.0004725). Homozygotes of this variant have been reported exclusively in Finnish patients with GRACILE syndrome. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000763070 SCV000893576 pathogenic Pili torti-deafness syndrome; GRACILE syndrome; Leigh syndrome; Mitochondrial complex III deficiency, nuclear type 1 2018-10-31 criteria provided, single submitter clinical testing
OMIM RCV000006542 SCV000026725 pathogenic GRACILE syndrome 2002-10-01 no assertion criteria provided literature only
Counsyl RCV000983982 SCV000678004 pathogenic Mitochondrial complex III deficiency, nuclear type 1 2015-07-21 no assertion criteria provided clinical testing
Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes RCV000519547 SCV000778193 pathogenic not provided 2016-03-08 no assertion criteria provided clinical testing

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