ClinVar Miner

Submissions for variant NM_014363.6(SACS):c.6857A>G (p.Lys2286Arg)

gnomAD frequency: 0.00001  dbSNP: rs754381972
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000791527 SCV000930780 uncertain significance Spastic paraplegia 2021-08-25 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 2286 of the SACS protein (p.Lys2286Arg). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and arginine. This variant is present in population databases (rs754381972, ExAC 0.003%). This variant has not been reported in the literature in individuals affected with SACS-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Natera, Inc. RCV001275190 SCV001460049 uncertain significance Charlevoix-Saguenay spastic ataxia 2020-01-17 no assertion criteria provided clinical testing

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