Submissions for variant NM_015046.7(SETX):c.8C>T (p.Thr3Ile)

dbSNP: rs28941475

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000414273	SCV000491150	likely pathogenic	not provided	2016-08-02	criteria provided, single submitter	clinical testing	The T3I variant in the SETX gene has been reported previously in multiple families in association with hereditary motor neuropathies (Chen et al., 2004; Arning et al., 2013; Drew et al., 2015). The T3I 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. The T3I variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. The T3I variant is a strong candidate for a pathogenic variant.
OMIM	RCV000002380	SCV000022538	pathogenic	Amyotrophic lateral sclerosis type 4	2004-06-01	no assertion criteria provided	literature only
Northcott Neuroscience Laboratory, ANZAC Research Institute	RCV000002380	SCV000188713	pathogenic	Amyotrophic lateral sclerosis type 4		no assertion criteria provided	not provided	Converted during submission to Pathogenic.
Inherited Neuropathy Consortium	RCV000789614	SCV000928979	uncertain significance	Distal spinal muscular atrophy		no assertion criteria provided	literature only
Inherited Neuropathy Consortium Ii, University Of Miami	RCV000002380	SCV004011926	uncertain significance	Amyotrophic lateral sclerosis type 4	2016-01-06	no assertion criteria provided	literature only