ClinVar Miner

Submissions for variant NM_001079866.2(BCS1L):c.349C>T (p.Arg117Ter)

gnomAD frequency: 0.00001  dbSNP: rs777735526
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000409388 SCV000485697 likely pathogenic GRACILE syndrome 2016-02-02 criteria provided, single submitter clinical testing
Invitae RCV001357982 SCV002151158 pathogenic not provided 2021-10-16 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with BCS1L-related conditions. ClinVar contains an entry for this variant (Variation ID: 370387). This variant is present in population databases (rs777735526, ExAC 0.003%). This sequence change creates a premature translational stop signal (p.Arg117*) in the BCS1L gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BCS1L are known to be pathogenic (PMID: 17314340, 25895478).
Baylor Genetics RCV003475945 SCV004210790 likely pathogenic Pili torti-deafness syndrome 2023-09-20 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001357982 SCV001553598 likely pathogenic not provided no assertion criteria provided clinical testing The BCS1L p.Arg117* variant was not identified in the literature nor was it identified in LOVD 3.0. The variant was identified in dbSNP (ID: rs777735526) and ClinVar (classified as likely pathogenic by Counsyl for GRACILE syndrome). The variant was identified in control databases in 3 of 251496 chromosomes at a frequency of 0.00001193 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the European (non-Finnish) population in 3 of 113770 chromosomes (freq: 0.000026), but was not observed in the African, Latino, Ashkenazi Jewish, East Asian, European (Finnish), Other or South Asian populations. The c.349C>T variant leads to a premature stop codon at position 117 which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the BCS1L gene are an established mechanism of disease in BCS1L-Related Disorders and are the type of variant expected to cause the disorder when found in the homozygous or compound heterozygous state. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more pathogenic role for this variant. This variant is classified as likely pathogenic.

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