Submissions for variant NM_000169.3(GLA):c.901C>T (p.Arg301Ter)

dbSNP: rs398123224

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000157879	SCV000110141	pathogenic	not provided	2015-03-05	criteria provided, single submitter	clinical testing
GeneDx	RCV000157879	SCV000207810	pathogenic	not provided	2021-06-10	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (Lek et al., 2016); Nonsense 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; This variant is associated with the following publications: (PMID: 15713906, 15776423, 27560961, 28679849, 27535533, 25525159, 15806320, 11668641, 12428061, 8996967, 27899143, 27156739, 26602202, 18651238, 23935525, 28090261, 28728877, 27773586, 31996269, 7531540)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000781418	SCV000919436	pathogenic	Fabry disease	2019-07-03	criteria provided, single submitter	clinical testing	Variant summary: GLA c.901C>T (p.Arg301X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 183457 control chromosomes (gnomAD). c.901C>T has been reported in the literature in multiple individuals affected with Fabry Disease (Bowman_2013, Lukas_2013, Schafer_2005, Ries_2005, Blaydon_2001, Nakano_2013, Shin_2008). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity (Shin_2008, Ries_2005). Two ClinVar submissions (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae	RCV000781418	SCV001590650	pathogenic	Fabry disease	2023-07-28	criteria provided, single submitter	clinical testing	This premature translational stop signal has been observed in individuals with Fabry disease (PMID: 7531540, 28728877). ClinVar contains an entry for this variant (Variation ID: 92570). For these reasons, this variant has been classified as Pathogenic. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg301*) in the GLA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GLA are known to be pathogenic (PMID: 10666480, 12175777).
Revvity Omics, Revvity	RCV000157879	SCV002024294	pathogenic	not provided	2022-12-14	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000781418	SCV002054394	pathogenic	Fabry disease	2021-07-15	criteria provided, single submitter	clinical testing
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	RCV000781418	SCV004101116	pathogenic	Fabry disease	2023-11-02	no assertion criteria provided	clinical testing