ClinVar Miner

Submissions for variant NM_183075.3(CYP2U1):c.343G>A (p.Gly115Ser)

gnomAD frequency: 0.00001  dbSNP: rs766889023
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001379753 SCV001577613 likely pathogenic Spastic paraplegia 2021-02-22 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 115 of the CYP2U1 protein (p.Gly115Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs766889023, ExAC 0.01%). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 CYP2U1 protein function. This variant has been observed in individual(s) with hereditary spastic paraplegia (PMID: 29034544). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001847253 SCV002104522 likely pathogenic Hereditary spastic paraplegia 2021-06-10 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV002276241 SCV002563818 pathogenic not provided 2020-10-01 criteria provided, single submitter clinical testing

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