Submissions for variant NM_001371279.1(REEP1):c.211G>A (p.Ala71Thr)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003601531	SCV004410754	uncertain significance	Hereditary spastic paraplegia 31	2023-05-30	criteria provided, single submitter	clinical testing	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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with REEP1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 71 of the REEP1 protein (p.Ala71Thr).
Concord Molecular Medicine Laboratory, Concord Repatriation General Hospital	RCV003601531	SCV005199851	uncertain significance	Hereditary spastic paraplegia 31	2024-08-20	criteria provided, single submitter	clinical testing	This variant was detected in a heterozygous state in a patient with lower limb spasticity and hyperreflexia. Normal brain and spine MRI. This variant is absent from control population (gnomAD v4.1.0). It has been reported as a variant of uncertain significance previously on ClinVar. In silico analysis suggested this variant to be pathogenic (REVEL 0.87).