Submissions for variant NM_014845.6(FIG4):c.759del (p.Phe254fs)

dbSNP: rs764717219

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Weber Lab, Hannover Medical School	RCV000416492	SCV000299295	pathogenic	Amyotrophic lateral sclerosis type 11	2016-09-13	criteria provided, single submitter	research
Athena Diagnostics	RCV000517693	SCV000613305	pathogenic	not provided	2017-02-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000533386	SCV000657870	pathogenic	Charcot-Marie-Tooth disease type 4	2023-12-09	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Phe254Serfs*8) in the FIG4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FIG4 are known to be pathogenic (PMID: 23623387, 30740813). This variant is present in population databases (rs764717219, gnomAD 0.007%). This premature translational stop signal has been observed in individuals with autosomal recessive Charcot-Marie-Tooth disease (PMID: 17572665, 21705420). ClinVar contains an entry for this variant (Variation ID: 254668). For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV000517693	SCV001246356	pathogenic	not provided	2016-11-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000517693	SCV002099568	pathogenic	not provided	2024-08-21	criteria provided, single submitter	clinical testing	Identified by whole exome sequencing in the heterozygous state in an individual with ALS; however, the variant was identified in his unaffected father and other affected relatives were not available for molecular testing to establish segregation (PMID: 28051077); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 21705420, 31589614, 32376792, 17572665, 28051077)
OMIM	RCV000001795	SCV000021951	pathogenic	Charcot-Marie-Tooth disease type 4J	2007-07-05	no assertion criteria provided	literature only
Inherited Neuropathy Consortium	RCV000789114	SCV000928465	uncertain significance	Charcot-Marie-Tooth disease		no assertion criteria provided	literature only
Inherited Neuropathy Consortium Ii, University Of Miami	RCV000001795	SCV004174431	uncertain significance	Charcot-Marie-Tooth disease type 4J	2016-01-06	no assertion criteria provided	literature only