ClinVar Miner

Submissions for variant NM_014845.5(FIG4):c.2467C>T (p.Gln823Ter) (rs745790694)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000518350 SCV000613300 likely pathogenic not provided 2017-07-11 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000825523 SCV000966838 likely pathogenic Charcot-Marie-Tooth disease, type 4J 2018-06-15 criteria provided, single submitter clinical testing The p.Gln823X variant in FIG4 has been reported in 1 individual with a suspicion of Charcot-Marie-Tooth (CMT; Nicholson 2011) and in ClinVar (Variation ID: 4473 36). This variant has been identified in 6/126658 European chromosomes by the Ge nome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs745 790694). This nonsense variant leads to a premature termination codon at positio n 823, which is predicted to lead to a truncated or absent protein. CMT Type 4J is caused by biallelic compound heterozygous pathogenic variants in FIG4, most c ommonly when one is a missense variant and the other a loss-of-function variant (Nicholson 2011). Biallelic pathogenic variants that cause complete loss of FIG4 function is associated with Yunis-Varon syndrome (YVS) (Campeau 2013). In summa ry, although additional studies are required to fully establish its clinical sig nificance, this variant is likely pathogenic. ACMG/AMP Criteria applied: PVS1_Ve ryStrong; PM2.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000518350 SCV001154851 likely pathogenic not provided 2016-06-01 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001197829 SCV001368609 pathogenic Yunis-Varon syndrome 2020-04-02 criteria provided, single submitter clinical testing This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PS4_Mod,PM2.
Invitae RCV001216587 SCV001388391 pathogenic Charcot-Marie-Tooth disease type 4 2019-08-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln823*) in the FIG4 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs745790694, ExAC 0.001%). This variant has been observed in an individual who underwent genetic testing for Charcot-Marie-Tooth disease (PMID: 21705420). ClinVar contains an entry for this variant (Variation ID: 447336). Loss-of-function variants in FIG4 are known to be pathogenic (PMID: 23623387). For these reasons, this variant has been classified as Pathogenic.
Inherited Neuropathy Consortium RCV000789755 SCV000929134 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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