Submissions for variant NM_022834.5(VWA1):c.62_71dup (p.Gly25fs)

dbSNP: rs749383814

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Fulgent Genetics, Fulgent Genetics	RCV001310232	SCV002813987	pathogenic	Neuronopathy, distal hereditary motor, autosomal recessive 7	2022-04-26	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003222198	SCV003916032	pathogenic	not provided	2023-03-01	criteria provided, single submitter	clinical testing	VWA1: PVS1, PM2, PM3
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	RCV001310232	SCV004046344	pathogenic	Neuronopathy, distal hereditary motor, autosomal recessive 7		criteria provided, single submitter	clinical testing	This frameshifting variant in exon 1 of 3 is predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay (NMD). This variant has been previously reported as a compound heterozygous or homozygous change in individuals with neuromyopathy (PMID: 33459760) and hereditary motor neuropathy (PMID: 33559681). The c.62_71dup (p.Gly25ArgfsTer74) variant is present in the heterozygous state in the gnomAD population database at a frequency of 0.0333% (15/45050) and thus is presumed to be rare. Based on the available evidence, the c.62_71dup (p.Gly25ArgfsTer74) variant is classified as Pathogenic.
PreventionGenetics, part of Exact Sciences	RCV003413814	SCV004118453	likely pathogenic	VWA1-related disorder	2022-09-16	criteria provided, single submitter	clinical testing	The VWA1 c.62_71dup10 variant is predicted to result in a frameshift and premature protein termination (p.Gly25Argfs*74). This variant has been reported in the compound heterozygous and homozygous state in individuals from mutliple unrelated families with neuromyopathy (Deschauer et al 2021. PubMed ID: 33459760; Pagnamenta AT et al 2021. PubMed ID: 33559681). This variant is reported in 0.070% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-1371178-T-TGGCGCGGAGC). Frameshift variants in VWA1 are expected to be pathogenic. This variant is interpreted as likely pathogenic.
Neurogenomics Lab, Neuroscience Institute, University Of Cape Town	RCV001310232	SCV004171120	pathogenic	Neuronopathy, distal hereditary motor, autosomal recessive 7	2024-05-22	criteria provided, single submitter	research	Sequencing funded by the International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD): https://www.ucl.ac.uk/genomic-medicine-neuromuscular-diseases/.
Baylor Genetics	RCV001310232	SCV005049489	pathogenic	Neuronopathy, distal hereditary motor, autosomal recessive 7	2024-02-05	criteria provided, single submitter	clinical testing
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV003222198	SCV005199021	likely pathogenic	not provided	2023-01-12	criteria provided, single submitter	clinical testing
Section for Clinical Neurogenetics, University of Tübingen	RCV001839418	SCV001190597	likely pathogenic	Neuromuscular disease	2020-01-01	no assertion criteria provided	research
OMIM	RCV001310232	SCV001499846	pathogenic	Neuronopathy, distal hereditary motor, autosomal recessive 7	2023-10-17	no assertion criteria provided	literature only