Submissions for variant NM_014855.3(AP5Z1):c.2053C>T (p.Arg685Cys)

gnomAD frequency: 0.00017  dbSNP: rs367867460

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Unit for Genetic & Epidemiological Research on Neurological Disorders, Instituto de Investigação e Inovação em Saúde	RCV000516094	SCV000574502	uncertain significance	Hereditary spastic paraplegia	2017-03-07	criteria provided, single submitter	research
Athena Diagnostics	RCV000710601	SCV000840844	uncertain significance	not provided	2018-01-03	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001344614	SCV001538678	uncertain significance	Hereditary spastic paraplegia 48	2022-08-31	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 685 of the AP5Z1 protein (p.Arg685Cys). This variant is present in population databases (rs367867460, gnomAD 0.05%). This missense change has been observed in individual(s) with clinical features of spastic paraplegia (PMID: 28832565). ClinVar contains an entry for this variant (Variation ID: 424688). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV000516094	SCV002106172	uncertain significance	Hereditary spastic paraplegia	2017-04-12	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000710601	SCV002821796	uncertain significance	not provided	2022-11-01	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001344614	SCV003835815	uncertain significance	Hereditary spastic paraplegia 48	2022-10-10	criteria provided, single submitter	clinical testing
GenomeConnect, ClinGen	RCV001344614	SCV002074990	not provided	Hereditary spastic paraplegia 48		no assertion provided	phenotyping only	Variant interpreted as Uncertain significance and reported on 01-03-2018 by Lab or GTR ID 1012. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.