Submissions for variant NM_002863.5(PYGL):c.1145C>T (p.Pro382Leu)

gnomAD frequency: 0.00440  dbSNP: rs143759519

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000625936	SCV000746525	uncertain significance	Glycogen storage disease, type VI	2017-12-03	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000625936	SCV000896401	uncertain significance	Glycogen storage disease, type VI	2018-10-31	criteria provided, single submitter	clinical testing
Invitae	RCV000625936	SCV001105556	likely benign	Glycogen storage disease, type VI	2024-01-13	criteria provided, single submitter	clinical testing
Mendelics	RCV000625936	SCV001139455	benign	Glycogen storage disease, type VI	2023-08-22	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000625936	SCV001271641	uncertain significance	Glycogen storage disease, type VI	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Institute of Human Genetics, University of Leipzig Medical Center	RCV000625936	SCV001439985	uncertain significance	Glycogen storage disease, type VI	2019-01-01	criteria provided, single submitter	clinical testing	This variant was identified as compound heterozygous.
Baylor Genetics	RCV000625936	SCV001522874	uncertain significance	Glycogen storage disease, type VI	2019-11-14	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
CeGaT Center for Human Genetics Tuebingen	RCV003311865	SCV004010281	likely benign	not provided	2023-07-01	criteria provided, single submitter	clinical testing	PYGL: PP3, BS2
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003488738	SCV004241565	likely benign	not specified	2023-12-21	criteria provided, single submitter	clinical testing	Variant summary: PYGL c.1145C>T (p.Pro382Leu) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0041 in 251388 control chromosomes in the gnomAD database, including 6 homozygotes. c.1145C>T has been reported in the literature at a compound heterozygous state along with a second pathogenic missense in an individual affected with Glycogen storage disease (example, Davit-Spraul_2011). These report(s) do not provide unequivocal conclusions about association of the variant with Glycogen storage disease, type VI. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 21646031). Eight submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Multiple submitters reported the variant with conflicting assessments (Benign/Likely benign, n=3; VUS, n=5). Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV003917992	SCV004730595	likely benign	PYGL-related condition	2020-03-26	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).