ClinVar Miner

Submissions for variant NM_025137.4(SPG11):c.1383G>T (p.Gln461His)

gnomAD frequency: 0.00001  dbSNP: rs932177370
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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 RCV000531513 SCV000642211 uncertain significance Hereditary spastic paraplegia 11 2022-08-09 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 461 of the SPG11 protein (p.Gln461His). This variant is not present in population databases (gnomAD no frequency). 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: 466504). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0". The histidine 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.
Ambry Genetics RCV002384151 SCV002696484 uncertain significance Inborn genetic diseases 2019-12-28 criteria provided, single submitter clinical testing The p.Q461H variant (also known as c.1383G>T), located in coding exon 6 of the SPG11 gene, results from a G to T substitution at nucleotide position 1383. The glutamine at codon 461 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and histidine 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.

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