ClinVar Miner

Submissions for variant NM_014846.4(WASHC5):c.1772C>T (p.Ser591Phe) (rs1554593899)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center of Genomic medicine, Geneva,University Hospital of Geneva RCV000585718 SCV000693455 likely pathogenic Hereditary spastic paraplegia 8 2017-08-07 criteria provided, single submitter clinical testing
Invitae RCV001069360 SCV001234524 uncertain significance Hereditary spastic paraplegia 8; Ritscher-Schinzel syndrome 2019-12-19 criteria provided, single submitter clinical testing This sequence change replaces serine with phenylalanine at codon 591 of the WASHC5 protein (p.Ser591Phe). The serine residue is moderately conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of hereditary spastic paraplegia (Invitae). ClinVar contains an entry for this variant (Variation ID: 495056). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Ser591 amino acid residue in WASHC5. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 24824269). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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