ClinVar Miner

Submissions for variant NM_014363.6(SACS):c.8238_8239dup (p.Ile2747fs)

dbSNP: rs779248938
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV001287920 SCV001474685 likely pathogenic not provided 2019-09-26 criteria provided, single submitter clinical testing The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. The frequency of this variant in the general population is consistent with pathogenicity.
Invitae RCV003750860 SCV004533801 pathogenic Spastic paraplegia 2023-10-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ile2747Lysfs*7) in the SACS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1833 amino acid(s) of the SACS protein. This variant is present in population databases (rs779248938, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with SACS-related conditions. ClinVar contains an entry for this variant (Variation ID: 994462). This variant disrupts a region of the SACS protein in which other variant(s) (p.Asn4549Asp) have been determined to be pathogenic (PMID: 15156359, 21507954). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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