Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000218755 | SCV000279619 | pathogenic | not provided | 2016-02-29 | criteria provided, single submitter | clinical testing | The P285L missense variant in the TFG gene has been previously reported to segregate with proximal hereditary motor and sensory neuropathy (HMSN-P) in several large families (Lee et al., 2013, Ishiura et al., 2012, Alavi et al., 2015). Functional studies demonstrate the P285L disrupts the protein and leads to inclusion body formation in cultured cells (Ishiura et al., 2012). It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The P285L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals. |
Lupski Lab, |
RCV000030736 | SCV000292367 | pathogenic | Hereditary motor and sensory neuropathy, Okinawa type | 2015-08-18 | criteria provided, single submitter | research | This variant has been previously reported as disease-causing and was found in an individual with peripheral neuropathy. |
Invitae | RCV000642397 | SCV000764067 | pathogenic | Hereditary motor and sensory neuropathy, Okinawa type; Spastic paraplegia 57, autosomal recessive | 2018-07-25 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with leucine at codon 285 of the TFG protein (p.Pro285Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) in multiple families (PMID: 22883144, 23553329, 25725944). ClinVar contains an entry for this variant (Variation ID: 37089). Experimental studies have shown that this missense change leads to cytoplasmic aggregation of TDP-43 (PMID: 22883144) and impacts the ubiquitin-proteasome system (PMID: 24613659, 28196470). For these reasons, this variant has been classified as Pathogenic. |
Mendelics | RCV000030736 | SCV001136563 | pathogenic | Hereditary motor and sensory neuropathy, Okinawa type | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Suna and Inan Kirac Foundation Neurodegeneration Research Laboratory, |
RCV001095428 | SCV001251006 | likely pathogenic | Amyotrophic Lateral Sclerosis with Sensory Neuropathy | 2020-03-31 | criteria provided, single submitter | research | |
OMIM | RCV000030736 | SCV000053397 | pathogenic | Hereditary motor and sensory neuropathy, Okinawa type | 2013-05-01 | no assertion criteria provided | literature only |