ClinVar Miner

Submissions for variant NM_015915.5(ATL1):c.740A>G (p.His247Arg)

dbSNP: rs2140226883
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute for Human Genetics and Genomic Medicine, Uniklinik RWTH Aachen RCV001376177 SCV001573127 likely pathogenic Hereditary spastic paraplegia 3A 2021-05-05 criteria provided, single submitter clinical testing To our knowledge, this sequence variant has not been reported in the literature or in control databases. However, a sequence variant affecting the same nuceotide, c.740A>C, p.(His247Pro), has previously been reported as causing SPG3 (Nameka 2006, Abel, 2004). The detected variant segregates with the disease in the family. We therefore classify it as being likely pathogenic.
Invitae RCV001376177 SCV003442284 uncertain significance Hereditary spastic paraplegia 3A 2022-09-17 criteria provided, single submitter clinical testing 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. This variant disrupts the p.His247 amino acid residue in ATL1. Other variant(s) that disrupt this residue have been observed in individuals with ATL1-related conditions (PMID: 14695538), which suggests that this may be a clinically significant amino acid residue. 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. ClinVar contains an entry for this variant (Variation ID: 1065628). This missense change has been observed in individual(s) with ATL1-related conditions (PMID: 19459885, 26671083). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 247 of the ATL1 protein (p.His247Arg).

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