ClinVar Miner

Submissions for variant NM_025137.4(SPG11):c.6481C>T (p.Arg2161Trp)

gnomAD frequency: 0.00003  dbSNP: rs773954273
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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 RCV000642570 SCV000764257 uncertain significance Hereditary spastic paraplegia 11 2022-07-19 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 2161 of the SPG11 protein (p.Arg2161Trp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 534873). 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: "Probably Damaging"; Align-GVGD: "Class C15"). 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 RCV002358826 SCV002656060 uncertain significance Inborn genetic diseases 2022-08-30 criteria provided, single submitter clinical testing The c.6481C>T (p.R2161W) alteration is located in exon 35 (coding exon 35) of the SPG11 gene. This alteration results from a C to T substitution at nucleotide position 6481, causing the arginine (R) at amino acid position 2161 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV004822143 SCV005443062 uncertain significance not provided 2024-07-05 criteria provided, single submitter clinical testing 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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