Submissions for variant NM_000169.3(GLA):c.337_354del (p.Phe113_Arg118del)

dbSNP: rs2147480442

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine	RCV001537870	SCV001754804	pathogenic	Fabry disease	2019-11-07	criteria provided, single submitter	clinical testing	The c.337_354del (p.Phe113_Arg118del) variant in the GLA gene is an in-frame deletion of 18 bp that is predicted to shorten the encoded protein by 6 amino acids but does not introduce a frameshift. Also known as c.333del18, this variant is a known pathogenic variant associated with the classic Fabry phenotype (PMID: 7531540). It is absent from general population databases. We consider this variant is to be pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001537870	SCV004299647	pathogenic	Fabry disease	2023-02-25	criteria provided, single submitter	clinical testing	This variant, c.337_354del, results in the deletion of 6 amino acid(s) of the GLA protein (p.Phe113_Arg118del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with Fabry disease (PMID: 7531540; Invitae). ClinVar contains an entry for this variant (Variation ID: 1180491). This variant disrupts a region of the GLA protein in which other variant(s) (p.Phe113Leu) have been determined to be pathogenic (PMID: 16773563, 17555407, 32099817). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.