ClinVar Miner

Submissions for variant NM_025137.4(SPG11):c.1780A>G (p.Ile594Val)

gnomAD frequency: 0.00001  dbSNP: rs762177930
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000706785 SCV000835855 uncertain significance Hereditary spastic paraplegia 11 2022-03-28 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 594 of the SPG11 protein (p.Ile594Val). This variant is present in population databases (rs762177930, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with SPG11-related conditions. ClinVar contains an entry for this variant (Variation ID: 582658). 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 tolerated. 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.
Ambry Genetics RCV004965710 SCV005504078 uncertain significance Inborn genetic diseases 2024-06-26 criteria provided, single submitter clinical testing The c.1780A>G (p.I594V) alteration is located in exon 9 (coding exon 9) of the SPG11 gene. This alteration results from a A to G substitution at nucleotide position 1780, causing the isoleucine (I) at amino acid position 594 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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