ClinVar Miner

Submissions for variant NM_020919.4(ALS2):c.575C>T (p.Pro192Leu)

gnomAD frequency: 0.00001  dbSNP: rs778003334
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Paris Brain Institute, Inserm - ICM RCV001391370 SCV001451106 pathogenic Infantile-onset ascending hereditary spastic paralysis criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001391370 SCV002167597 uncertain significance Infantile-onset ascending hereditary spastic paralysis 2022-10-19 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 988998). 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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on ALS2 function (PMID: 30224357). 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 ALS2 protein function. This missense change has been observed in individual(s) with amyotrophic lateral sclerosis (PMID: 28160950, 30581417). This variant is present in population databases (rs778003334, gnomAD 0.009%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 192 of the ALS2 protein (p.Pro192Leu).

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