ClinVar Miner

Submissions for variant NM_001304481.1(FGD4):c.2132_2136AAAAG[2] (p.Lys715fs) (rs751035912)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484688 SCV000566814 pathogenic not provided 2017-02-21 criteria provided, single submitter clinical testing The c.1887_1891delAAAAG variant was identified after homozygosity mapping in an individual with autosomal recessive Charcot Marie tooth disease (ARCMT); however no additional information was provided (Zimon et al., 2015). The c.1887_1891delAAAAG variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The c.1887_1891delAAAAG variant in the FGD4 gene causes a frameshift starting with codon Lysine 630, changes this amino acid to a Asparagine residue and creates a premature Stop codon at position 5 of the new reading frame, denoted p.K630NfsX5. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Therefore, the c.1887_1891delAAAAG variant is considered to be a pathogenic variant.
Invitae RCV001047299 SCV001211247 pathogenic Charcot-Marie-Tooth disease type 4 2019-04-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys630Asnfs*5) in the FGD4 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs779728254, ExAC 0.02%). This variant has been observed in an individual affected with Charcot-Marie-Tooth disease (PMID: 25231362). ClinVar contains an entry for this variant (Variation ID: 419181). Loss-of-function variants in FGD4 are known to be pathogenic (PMID: 17564972). For these reasons, this variant has been classified as Pathogenic.
Inherited Neuropathy Consortium RCV000789112 SCV000928463 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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