ClinVar Miner

Submissions for variant NM_025137.4(SPG11):c.496C>G (p.Leu166Val)

gnomAD frequency: 0.00001  dbSNP: rs372037097
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000805880 SCV000945855 uncertain significance Hereditary spastic paraplegia 11 2022-07-08 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 166 of the SPG11 protein (p.Leu166Val). This variant is present in population databases (rs372037097, 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: 650682). 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: "Tolerated"; 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. 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 RCV002336638 SCV002643450 uncertain significance Inborn genetic diseases 2020-12-30 criteria provided, single submitter clinical testing The p.L166V variant (also known as c.496C>G), located in coding exon 3 of the SPG11 gene, results from a C to G substitution at nucleotide position 496. The leucine at codon 166 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV003228994 SCV003926024 uncertain significance not provided 2022-11-22 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 26556829)

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