ClinVar Miner

Submissions for variant NM_014845.5(FIG4):c.831_838del (p.Lys278fs) (rs786200937)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236453 SCV000293532 pathogenic not provided 2019-01-08 criteria provided, single submitter clinical testing The c.831_838delTAAATTTG variant in the FIG4 gene has been previously reported in association with CMT4J as well as Yunis-Varon syndrome (Nicholson et al., 2011; Cottenie et al., 2013; Campeau et al., 2013). All affected individuals were compound heterozygous for c.831_838delTAAATTTG and another variant in the FIG4 gene. The c.831_838delTAAATTTG variant causes a frameshift starting with codon Lysine 278, changes this amino acid to a Tryptophan residue, and creates a premature Stop codon at position 6 of the new reading frame, denoted p.Lys278TrpfsX6. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. This variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, we interpret c.831_838delTAAATTTG as a pathogenic variant.
Invitae RCV001248346 SCV001421822 pathogenic Charcot-Marie-Tooth disease type 4 2019-01-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys278Trpfs*6) in the FIG4 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in several individuals affected with FIG4-related disease and to segregate with disease in a family (PMID: 21705420, 23489662, 23623387). ClinVar contains an entry for this variant (Variation ID: 50995). Loss-of-function variants in FIG4 are known to be pathogenic (PMID: 23623387). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000043691 SCV000071702 pathogenic Yunis-Varon syndrome 2013-05-02 no assertion criteria provided literature only
Service de Génétique Moléculaire,Hôpital Robert Debré RCV001255783 SCV001432396 pathogenic Polymicrogyria, bilateral temporooccipital no assertion criteria provided clinical testing

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