ClinVar Miner

Submissions for variant NM_015346.4(ZFYVE26):c.2639T>C (p.Leu880Pro)

dbSNP: rs2039789225
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002560270 SCV003442339 pathogenic Spastic paraplegia 2022-08-12 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 932301). This missense change has been observed in individual(s) with hereditary spastic paraplegia (PMID: 26492578). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 880 of the ZFYVE26 protein (p.Leu880Pro).
Institute of Human Genetics, University of Goettingen RCV001200049 SCV001245463 likely pathogenic Hereditary spastic paraplegia 15 2020-05-04 no assertion criteria provided clinical testing For the following reasons, the homozygous variant is assessed by us as a likely pathogenic variant: 1. the mutation is already described in affected patients with spastic paraplegia 15 (HGMD CM 167983, Kancheva et al., PMID: 26492578). 2. a comparison with the ExAC and gnomAD databases did not provide any indication that this sequence change is a norm variant that can also be detected in non-affected individuals and has a pathogenic computational verdict due to 4 pathogenic predictions from M-CAP, MutationTaster, Polyphen and SIFT

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