ClinVar Miner

Submissions for variant NM_025137.4(SPG11):c.3586C>T (p.Arg1196Cys)

gnomAD frequency: 0.00001  dbSNP: rs767936997
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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 RCV001887477 SCV002161049 uncertain significance Hereditary spastic paraplegia 11 2021-09-08 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 1196 of the SPG11 protein (p.Arg1196Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs767936997, ExAC 0.009%). This variant has not been reported in the literature in individuals affected with SPG11-related conditions. 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). 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 RCV004041599 SCV004955038 uncertain significance Inborn genetic diseases 2023-11-29 criteria provided, single submitter clinical testing The c.3586C>T (p.R1196C) alteration is located in exon 21 (coding exon 21) of the SPG11 gene. This alteration results from a C to T substitution at nucleotide position 3586, causing the arginine (R) at amino acid position 1196 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV004762230 SCV005369046 uncertain significance not provided 2023-06-26 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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