Submissions for variant NM_014363.6(SACS):c.1941G>T (p.Lys647Asn)

gnomAD frequency: 0.00003  dbSNP: rs201021919

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001367103	SCV001563439	uncertain significance	Spastic paraplegia	2021-08-31	criteria provided, single submitter	clinical testing	This sequence change replaces lysine with asparagine at codon 647 of the SACS protein (p.Lys647Asn). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with clinical features of hereditary spastic paraplegia (Invitae). 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: "Benign"; Align-GVGD: "Class C0"). 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.
Al Jalila Children's Genomics Center, Al Jalila Childrens Speciality Hospital	RCV001732142	SCV001984405	uncertain significance	Charlevoix-Saguenay spastic ataxia	2021-03-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001732142	SCV002026539	uncertain significance	Charlevoix-Saguenay spastic ataxia	2021-09-05	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001847251	SCV002105005	uncertain significance	Hereditary spastic paraplegia	2020-01-01	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001732142	SCV002086727	uncertain significance	Charlevoix-Saguenay spastic ataxia	2020-01-29	no assertion criteria provided	clinical testing