Submissions for variant NM_000169.3(GLA):c.1235_1236del (p.Thr412fs)

dbSNP: rs797044777

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000179730	SCV000232024	pathogenic	not provided	2015-02-05	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000781423	SCV000919441	pathogenic	Fabry disease	2019-11-19	criteria provided, single submitter	clinical testing	Variant summary: GLA c.1235_1236delCT (p.Thr412SerfsX24+) causes a frameshift which results in an extension of the protein. The variant was absent in 183416 control chromosomes (gnomAD). c.1235_1236delCT has been reported in the literature in multiple individuals affected with Fabry Disease (Park_2009, Blaydon_2001, Juchniewicz_2018, McCloskey_2018). These data indicate that the variant is very likely to be associated with disease. A ClinVar submission (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae	RCV000781423	SCV001222317	pathogenic	Fabry disease	2023-12-11	criteria provided, single submitter	clinical testing	This sequence change results in a frameshift in the GLA gene (p.Thr412Serfs*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 18 amino acid(s) of the GLA protein and extend the protein by 19 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This frameshift has been observed in individual(s) with Fabry disease (PMID: 1668641, 16595074, 20505683, 22551898, 23935525, 28728877, 30386727; Invitae). ClinVar contains an entry for this variant (Variation ID: 198402). For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab	RCV000781423	SCV002054366	pathogenic	Fabry disease	2021-07-15	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000781423	SCV002787844	pathogenic	Fabry disease	2021-08-04	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000179730	SCV004235663	pathogenic	not provided	2023-02-22	criteria provided, single submitter	clinical testing