Submissions for variant NM_053274.3(GLMN):c.844_847del (p.Leu282fs)

dbSNP: rs773060450

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001196048	SCV001366477	pathogenic	Glomuvenous malformation	2016-01-01	criteria provided, single submitter	clinical testing	This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PP4,PP5.
PreventionGenetics, part of Exact Sciences	RCV003396808	SCV004119379	likely pathogenic	GLMN-related disorder	2023-05-04	criteria provided, single submitter	clinical testing	The GLMN c.844_847delTTAG variant is predicted to result in a frameshift and premature protein termination (p.Leu282Glnfs*10). This variant was reported in an individual with Glomuvenous malformations (reported as 842delAGTT in Figure 3, Brouillard et al 2002. PubMed ID: 11845407). This variant is reported in 0.020% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-92737097-GCTAA-G). In ClinVar, this variant was interpreted as pathogenic (https://www.ncbi.nlm.nih.gov/clinvar/variation/930408/). Frameshift variants in GLMN are expected to be pathogenic. This variant is interpreted as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001796382	SCV004292349	pathogenic	not provided	2023-01-13	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with glomuvenous malformations (PMID: 11845407). This variant is also known as 842delAGTT. ClinVar contains an entry for this variant (Variation ID: 930408). This sequence change creates a premature translational stop signal (p.Leu282Glnfs*10) in the GLMN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GLMN are known to be pathogenic (PMID: 23801931). This variant is present in population databases (rs773060450, gnomAD 0.02%).
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV001196048	SCV005417641	pathogenic	Glomuvenous malformation		criteria provided, single submitter	clinical testing	PM2_Supporting+PVS1+PP4
Clinical Genetics, Academic Medical Center	RCV001796382	SCV002034444	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001796382	SCV002037426	pathogenic	not provided		no assertion criteria provided	clinical testing