ClinVar Miner

Submissions for variant NM_003119.4(SPG7):c.1976A>G (p.Tyr659Cys)

gnomAD frequency: 0.00001  dbSNP: rs1052772091
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001837086 SCV002097445 uncertain significance not provided 2022-02-09 criteria provided, single submitter clinical testing 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; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 22571692, AKHTAR2021[ARTICLE])
Ambry Genetics RCV004968313 SCV005504113 uncertain significance Inborn genetic diseases 2024-09-18 criteria provided, single submitter clinical testing The c.1976A>G (p.Y659C) alteration is located in exon 15 (coding exon 15) of the SPG7 gene. This alteration results from a A to G substitution at nucleotide position 1976, causing the tyrosine (Y) at amino acid position 659 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV005095297 SCV005740195 uncertain significance Hereditary spastic paraplegia 7 2024-06-02 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 659 of the SPG7 protein (p.Tyr659Cys). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 1341590). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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.

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