Submissions for variant NM_003119.4(SPG7):c.878C>T (p.Ala293Val)

gnomAD frequency: 0.00003  dbSNP: rs201723702

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001848245	SCV002105899	uncertain significance	Hereditary spastic paraplegia	2018-01-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001885412	SCV002211660	uncertain significance	Hereditary spastic paraplegia 7	2022-06-20	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 293 of the SPG7 protein (p.Ala293Val). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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"). This variant has not been reported in the literature in individuals affected with SPG7-related conditions. This variant is present in population databases (rs201723702, gnomAD 0.02%).
PROSPAX: an integrated multimodal progression chart in spastic ataxias, Center for Neurology; Hertie-Institute for Clinical Brain Research	RCV001885412	SCV005044552	pathogenic	Hereditary spastic paraplegia 7	2022-01-01	criteria provided, single submitter	research