ClinVar Miner

Submissions for variant NM_003119.4(SPG7):c.1305G>T (p.Gln435His)

gnomAD frequency: 0.00003  dbSNP: rs559906913
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000196196 SCV000252325 uncertain significance not provided 2016-10-17 criteria provided, single submitter clinical testing The Q435H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The Q435H variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV005090010 SCV005818839 uncertain significance Hereditary spastic paraplegia 7 2024-04-15 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 435 of the SPG7 protein (p.Gln435His). This variant is present in population databases (rs559906913, gnomAD 0.006%). 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: 215212). 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.

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