ClinVar Miner

Submissions for variant NM_014363.6(SACS):c.4612A>G (p.Ile1538Val) (rs544249449)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000518100 SCV000614957 uncertain significance not specified 2016-11-16 criteria provided, single submitter clinical testing
Invitae RCV000547323 SCV000629467 uncertain significance Spastic paraplegia 2017-06-23 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 1538 of the SACS protein (p.Ile1538Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs544249449, ExAC 0.02%). This variant has not been reported in the literature in individuals with a SACS-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant has uncertain impact on SACS function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Natera, Inc. RCV001275196 SCV001460062 uncertain significance Charlevoix-Saguenay spastic ataxia 2020-01-17 no assertion criteria provided clinical testing

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