ClinVar Miner

Submissions for variant NM_001079866.2(BCS1L):c.232A>G (p.Ser78Gly)

gnomAD frequency: 0.00042  dbSNP: rs28937590
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Total submissions: 13
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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 2021-10-05 criteria provided, single submitter clinical testing 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); 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: 21274865, 22829922, 18386115, 31980526, 12547234, 27809283, 32637629, 12215968, 24466228)
Institute of Human Genetics, Klinikum rechts der Isar RCV000006542 SCV000680154 pathogenic GRACILE syndrome 2017-09-08 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp 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
Baylor Genetics RCV000006542 SCV001162935 pathogenic GRACILE syndrome criteria provided, single submitter clinical testing
Myriad Women's Health, Inc. RCV000006542 SCV001193863 pathogenic GRACILE syndrome 2019-12-09 criteria provided, single submitter clinical testing NM_004328.4(BCS1L):c.232A>G(S78G) is classified as pathogenic in the context of BCS1L-related disorders. Sources cited for classification include the following: PMID 12215968 and 21274865. Classification of NM_004328.4(BCS1L):c.232A>G(S78G) is based on the following criteria: This is a well-established pathogenic variant in the literature that has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.
Invitae RCV000519547 SCV001207152 pathogenic not provided 2021-11-14 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 78 of the BCS1L protein (p.Ser78Gly). This variant is present in population databases (rs28937590, gnomAD 0.4%). This missense change has been observed in individuals with clinical features of BCS1L-related conditions (PMID: 12215968, 12547234, 18386115, 19508421). It is commonly reported in individuals of Finnish ancestry (PMID: 12215968). ClinVar contains an entry for this variant (Variation ID: 6167). 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. Experimental studies have shown that this missense change affects BCS1L function (PMID: 12215968, 21274865). For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV000519547 SCV002064003 pathogenic not provided 2021-10-01 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
Natera, Inc. RCV000006542 SCV002076346 pathogenic GRACILE syndrome 2021-01-19 no assertion criteria provided clinical testing

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