ClinVar Miner

Submissions for variant NM_015915.5(ATL1):c.751C>A (p.Gln251Lys)

dbSNP: rs1595615134
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Paris Brain Institute, Inserm - ICM RCV001391393 SCV001451210 pathogenic Hereditary spastic paraplegia 3A criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001391393 SCV002299386 uncertain significance Hereditary spastic paraplegia 3A 2025-01-12 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 251 of the ATL1 protein (p.Gln251Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant hereditary spastic paraplegia (PMID: 15596607, 34983064). It has also been observed to segregate with disease in related individuals. This variant is also known as 919C>A. ClinVar contains an entry for this variant (Variation ID: 989016). Invitae Evidence 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 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 ATL1 protein function. This variant disrupts the p.Gln251 amino acid residue in ATL1. Other variant(s) that disrupt this residue have been observed in individuals with ATL1-related conditions (PMID: 31236401), which suggests that this may be a clinically significant amino acid residue. 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.
Inherited Neuropathy Consortium Ii, University Of Miami RCV001391393 SCV004011955 uncertain significance Hereditary spastic paraplegia 3A 2016-01-06 no assertion criteria provided literature only

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