Submissions for variant NM_003640.5(ELP1):c.2741C>T (p.Pro914Leu)

dbSNP: rs28939712

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000006460	SCV001478676	likely pathogenic	Familial dysautonomia	2021-01-07	criteria provided, single submitter	clinical testing	Variant summary: IKBKAP c.2741C>T (p.Pro914Leu) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 242538 control chromosomes (gnomAD). c.2741C>T has been reported in the literature in at least one compound heterozygous individual affected with Familial Dysautonomia (e.g. Leyne_2003). This patient, the first non-Ashkenazi Jewish individual reported with this disorder, has been cited multiple times in subsequent publications (e.g. Gold-von Simson_2008, Monaghan_2008, Rubin_2017). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
OMIM	RCV000006460	SCV000026643	pathogenic	Familial dysautonomia	2003-05-01	no assertion criteria provided	literature only
Inherited Neuropathy Consortium	RCV000789661	SCV000929034	uncertain significance	Charcot-Marie-Tooth disease		no assertion criteria provided	literature only