PREPL Gene Curation
- Katherine Lafferty
Analytics
Gene-disease assertions not curated here (add link or write note):
Disease | Congenital myasthenic syndrome, 22 |
|---|---|
Inheritance | Autosomal recessive |
Prevalence |
Source: Unknown. At least 600 families described in the literature (Congenital myasthenic syndrome: MedlinePlus Genetics ) |
Rapid or full curation? | Rapid Full |
GenCC (myasthenic syndrome, congenital, 22): Strong- Invitae; Moderate- Illumina, PanelApp Australia, Ambry OMIM: Myasthenic syndrome, congenital, 22; MIM 616224 | |
Clinical Validity Scoring Notes and points | Variant/Case Evidence: PMID: 24610330 (Regal 2014): One proband, with myasthenic syndrome with paternally inherited deletion involving the PREPL gene and a maternally inherited frameshift variant (c.807delT) (4 points) PMID: 34693706 (Sayol-Torres 2023): One proband with myasthenic syndrome with maternally inherited deletion involving the PREPL gene and a paternally inherited nonsense variant (c.1528C>T p.(Arg510Ter)) (4 points) PMID: 28726805 (Regal 2018): Series of 5 new probands with isolated PREPL deficiency (congential myasthenic syndrome) (Maxed out Points - >12) Proband 1: HOM (PREPL) 2p21(44559541-44571008) Hg19 (PREPL exon 10-5) Proband 2: HET (PREPL) 2p21(44562458-44568223) Hg19/HET (c.358_361delTTTG; p.Val121Ilefs*121) Proband 3: HET (SLC3A1, PREPL) 2p21(44545015-44556286) Hg19/HET (c.1604T > G; p.Leu535*) Proband 4: HET (PREPL, CAMKMT) 2p21 (PREPL exon 12-CAMKMT exon 2)/HET (c.883 C > T; p.Arg295*) Proband 5:HET (SLC3A1, PREPL, CAMKMT) (SLC3A1 exon 7-CAMKMT exon 2)/HET (c.1156-1 G > A; p.L386_K451del) PMID: 33233562- One paper reports homozygous missense variant in proband. (p.Arg647Gln) Segregation Evidence: Case/Control Evidence: Experimental Evidence: Source: |
Clinical Validity Points Total |
Source: |
Clinical Validity Classification Definitive (12pts) Strong (12pts) Moderate (7-11pts) Limited (0.1-6pts) No genetic evidence Refuted Disputed | Definitive (12 pts) Source: |
Molecular Mechanism Loss of function Gain of function Dominant negative Unknown Other | Loss of function
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Penetrance Complete (100%) High (≥80%) Moderate (<80% and >20%) Low (≤20%) (list source/PMID) |
Source: |
Age of Onset Congenital Pediatric Adolescent Adulthood Late adulthood (list source/PMID) |
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Severity |
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Clinical Features |
Sources: |
HPO Terms |
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Gene SOPs & Notes | LINK if SOP is a long document. Short notes if it is easy to digest. eg. Last known truncating variant |
Curation Summary |
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Case ID, Curator name, Date, Jira ticket link |
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