ClinVar Miner

Submissions for variant NM_025137.4(SPG11):c.820G>A (p.Val274Ile)

gnomAD frequency: 0.00002  dbSNP: rs543316224
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000642588 SCV000764275 uncertain significance Hereditary spastic paraplegia 11 2022-07-26 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 274 of the SPG11 protein (p.Val274Ile). This variant is present in population databases (rs543316224, gnomAD 0.004%). 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: 534890). 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 isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001849021 SCV002105786 uncertain significance Hereditary spastic paraplegia 2016-12-12 criteria provided, single submitter clinical testing
Ambry Genetics RCV002424450 SCV002681244 uncertain significance Inborn genetic diseases 2021-08-20 criteria provided, single submitter clinical testing The p.V274I variant (also known as c.820G>A), located in coding exon 4 of the SPG11 gene, results from a G to A substitution at nucleotide position 820. The valine at codon 274 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and isoleucine is the reference amino acid in other 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.
Genome-Nilou Lab RCV002467971 SCV002764205 uncertain significance Amyotrophic lateral sclerosis type 5 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002467972 SCV002764207 uncertain significance Charcot-Marie-Tooth disease axonal type 2X criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000642588 SCV002764208 uncertain significance Hereditary spastic paraplegia 11 criteria provided, single submitter clinical testing

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