Submissions for variant NM_014946.4(SPAST):c.1360G>A (p.Glu454Lys)

dbSNP: rs1553318230

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000823324	SCV000964178	pathogenic	Hereditary spastic paraplegia 4	2022-02-22	criteria provided, single submitter	clinical testing	Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SPAST protein function. ClinVar contains an entry for this variant (Variation ID: 665112). This missense change has been observed in individual(s) with hereditary spastic paraplegia (PMID: 20550563, 29691679, 31157359; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 454 of the SPAST protein (p.Glu454Lys). For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV000823324	SCV001150269	pathogenic	Hereditary spastic paraplegia 4	2018-03-21	criteria provided, single submitter	clinical testing
Paris Brain Institute, Inserm - ICM	RCV000823324	SCV001450980	pathogenic	Hereditary spastic paraplegia 4		criteria provided, single submitter	clinical testing
Duke University Health System Sequencing Clinic, Duke University Health System	RCV000823324	SCV003918970	pathogenic	Hereditary spastic paraplegia 4	2023-04-20	criteria provided, single submitter	research