ClinVar Miner

Submissions for variant NM_014946.4(SPAST):c.1322A>G (p.Asp441Gly)

dbSNP: rs121908512
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000006018 SCV001377346 pathogenic Hereditary spastic paraplegia 4 2023-07-17 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 441 of the SPAST protein (p.Asp441Gly). This missense change has been observed in individuals with hereditary spastic paraplegia (PMID: 11039577, 16788734, 17100993, 17971434). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 5664). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic.
Paris Brain Institute, Inserm - ICM RCV000006018 SCV001450977 pathogenic Hereditary spastic paraplegia 4 criteria provided, single submitter clinical testing
GeneDx RCV004719628 SCV005326029 pathogenic not provided 2023-12-18 criteria provided, single submitter clinical testing Reported previously in several family members with spastic paraplegia (PMID: 11039577); 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; This variant is associated with the following publications: (PMID: 30476002, 32989326, 11039577)
OMIM RCV000006018 SCV000026200 pathogenic Hereditary spastic paraplegia 4 2000-10-01 no assertion criteria provided literature only
Yale Center for Mendelian Genomics, Yale University RCV001849258 SCV002106918 uncertain significance Tics 2020-09-28 no assertion criteria provided literature only

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