ClinVar Miner

Submissions for variant NM_005993.5(TBCD):c.3125C>T (p.Pro1042Leu)

gnomAD frequency: 0.00001  dbSNP: rs760635077
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Total submissions: 4
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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 RCV000995891 SCV001150282 likely pathogenic Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome 2019-08-19 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV000995891 SCV001745867 uncertain significance Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome 2020-06-18 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001858824 SCV002311957 uncertain significance not provided 2022-08-16 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 1042 of the TBCD protein (p.Pro1042Leu). This variant is present in population databases (rs760635077, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with TBCD-related conditions. ClinVar contains an entry for this variant (Variation ID: 807701). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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.
GeneDx RCV001858824 SCV003935436 uncertain significance not provided 2022-12-25 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: 36527993)

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