ClinVar Miner

Submissions for variant NM_003119.4(SPG7):c.1067C>T (p.Thr356Met)

gnomAD frequency: 0.00001  dbSNP: rs754903980
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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 RCV000640980 SCV000762589 uncertain significance Hereditary spastic paraplegia 7 2022-07-11 criteria provided, single submitter clinical testing This variant is present in population databases (rs754903980, gnomAD 0.003%). This missense change has been observed in individual(s) with ataxia and spasticity (PMID: 24727571). ClinVar contains an entry for this variant (Variation ID: 533736). 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. 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. This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 356 of the SPG7 protein (p.Thr356Met).
GeneDx RCV004768497 SCV005380216 uncertain significance not provided 2024-04-19 criteria provided, single submitter clinical testing Identified in the heterozygous state in a patient with progressive external ophthalmoplegia, spasticity, and ataxia in published literature (PMID: 24727571); Published functional studies suggest that this variant may contribute to COX-deficient fiber and mitochondrial defects associated with progressive external ophthalmoplegia; however, additional studies are needed to validate the functional effect of this variant in vivo (PMID: 24727571); 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; This variant is associated with the following publications: (PMID: 22571692, 24727571, 31271879)

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