ClinVar Miner

Submissions for variant NM_003119.4(SPG7):c.1795C>T (p.Arg599Trp)

gnomAD frequency: 0.00002  dbSNP: rs764645740
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001370289 SCV001566760 uncertain significance Hereditary spastic paraplegia 7 2024-01-21 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 599 of the SPG7 protein (p.Arg599Trp). This variant is present in population databases (rs764645740, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SPG7-related conditions. ClinVar contains an entry for this variant (Variation ID: 1060812). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SPG7 protein function with a positive predictive value of 80%. 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.
GeneDx RCV001587379 SCV001824273 uncertain significance not provided 2023-06-06 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
Athena Diagnostics RCV001587379 SCV001879864 uncertain significance not provided 2020-11-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV003169900 SCV003884075 uncertain significance Inborn genetic diseases 2023-02-01 criteria provided, single submitter clinical testing The c.1795C>T (p.R599W) alteration is located in exon 14 (coding exon 14) of the SPG7 gene. This alteration results from a C to T substitution at nucleotide position 1795, causing the arginine (R) at amino acid position 599 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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