Submissions for variant NM_000520.4(HEXA):c.745C>T (p.Arg249Trp)

gnomAD frequency: 0.00019  dbSNP: rs138058578

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000190592	SCV000245618	other	Tay-Sachs disease	2014-05-30	criteria provided, single submitter	clinical testing	pseudodeficiency
Eurofins Ntd Llc (ga)	RCV000375852	SCV000331536	other	not provided	2016-07-19	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000375852	SCV000697174	benign	not provided	2016-08-11	criteria provided, single submitter	clinical testing	Variant summary: The HEXA c.745C>T (p.Arg249Trp) variant causes a missense change involving a conserved nucleotide with 5/5 in silico tools predicting a damaging outcome. The variant of interest was found in the large, broad control population, ExAC, with an allele frequency of 28/121408 (1/4336), which does not exceed the estimated maximal expected allele frequency for a pathogenic HEXA variant of 1/715. The variant of interest is known to be a common pseudodeficiency allele, which is not associated with neurologic disease but is associated wtih reduced degradation of the synthetic substrate when HEX A enzymatic activity is determined (Gene Reviews). Therefore, the variant of interest is classified as Benign.
Invitae	RCV000190592	SCV000933533	other	Tay-Sachs disease	2018-12-13	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000375852	SCV004698536	uncertain significance	not provided	2024-02-01	criteria provided, single submitter	clinical testing	HEXA: PM2:Supporting