ClinVar Miner

Submissions for variant NM_003119.4(SPG7):c.1931C>T (p.Thr644Ile)

dbSNP: rs758702550
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000520300 SCV000620688 likely pathogenic not provided 2017-09-14 criteria provided, single submitter clinical testing The T644I variant in the SPG7 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The T644I variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The T644I variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret T644I as a likely pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001066395 SCV001231402 uncertain significance Hereditary spastic paraplegia 7 2019-06-03 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 644 of the SPG7 protein (p.Thr644Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SPG7-related conditions. ClinVar contains an entry for this variant (Variation ID: 451927). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Athena Diagnostics RCV000520300 SCV002770738 uncertain significance not provided 2022-05-04 criteria provided, single submitter clinical testing

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