Submissions for variant NM_025137.4(SPG11):c.6367C>T (p.His2123Tyr)

dbSNP: rs1567129561

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000761909	SCV000892129	uncertain significance	not provided	2018-07-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001219818	SCV001391776	uncertain significance	Hereditary spastic paraplegia 11	2019-04-10	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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SPG11-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with tyrosine at codon 2123 of the SPG11 protein (p.His2123Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine.
Genome-Nilou Lab	RCV002468032	SCV002763720	uncertain significance	Amyotrophic lateral sclerosis type 5		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002468033	SCV002763721	uncertain significance	Charcot-Marie-Tooth disease axonal type 2X		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001219818	SCV002763722	uncertain significance	Hereditary spastic paraplegia 11		criteria provided, single submitter	clinical testing