ClinVar Miner

Submissions for variant NM_024306.5(FA2H):c.968C>T (p.Pro323Leu)

gnomAD frequency: 0.00003  dbSNP: rs774131656
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München RCV000995544 SCV001149772 pathogenic Hereditary spastic paraplegia 35 2019-06-07 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003588705 SCV004297029 pathogenic Spastic paraplegia 2023-12-11 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 323 of the FA2H protein (p.Pro323Leu). This variant is present in population databases (rs774131656, gnomAD 0.002%). This missense change has been observed in individual(s) with hereditary spastic paraplegia (PMID: 22965561, 31135052, 31407473, 35872528; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 807416). 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 FA2H protein function. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV004761855 SCV005369915 uncertain significance not provided 2024-04-04 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; This variant is associated with the following publications: (PMID: 24359114, 38275596, 22965561, 31407473, 31135052, 35872528)

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