Submissions for variant NM_005609.4(PYGM):c.2379+2_2379+3delinsAT

dbSNP: rs2135823216

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Revvity Omics, Revvity	RCV001784892	SCV002019576	pathogenic	Glycogen storage disease, type V	2021-06-22	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001784892	SCV003786525	pathogenic	Glycogen storage disease, type V	2022-08-04	criteria provided, single submitter	clinical testing	Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This sequence change affects a splice site in intron 19 of the PYGM gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. Disruption of this splice site has been observed in individual(s) with McArdle disease (PMID: 31080931). ClinVar contains an entry for this variant (Variation ID: 1323509). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). This variant disrupts a region of the PYGM protein in which other variant(s) (p.Trp798Arg) have been determined to be pathogenic (PMID: 17630210, 17994553, 21802952). 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.
Baylor Genetics	RCV001784892	SCV004207264	likely pathogenic	Glycogen storage disease, type V	2023-06-14	criteria provided, single submitter	clinical testing