Curation HMNR7 VWA1

Gene VWA1

Disease HMNR7

Inheritance AR

Score

12 + 0.5 = 12.5 / 18

Genetic + experimental = total

Classification

Definitive

Refuted

Moderate

Definitive

Last Updated 08/14/2025

Pubs Reviewed 3

Publication Span 3.08 years

Publication Interval 3.08 years

Curator(s) Macayla Weiner, Laurel Hiatt, Harriet Dashnow

Description

Biallelic VWA1 variants cause autosomal recessive hereditary motor neuropathy/neuromyopathy (HMNR7). The recurrent exon 1 10-bp repeat expansion c.62_71dup, p.(Gly25ArgfsTer74), is the predominant disease-associated allele and was reported in most families, often with loss-of-function consequences. Genetic support includes multiple unrelated affected families, trans/inheritance evidence for compound heterozygotes, and founder-haplotype/autozygosity evidence. Experimental support is mainly gene-level or patient-tissue evidence: WARP/VWA1 is an extracellular-matrix protein reported to interact with collagen VI and perlecan, and patient-derived blood or muscle tissue studies show neuromuscular biomarker/pathology changes.

All criTRia Curations Locus Page

Genetic evidence

Total: 12

Per page

Category	Type	Citation	Score	Details
Singular Evidence	Probands	PMID:33559681	6	17 affected individuals from 15 unrelated families with biallelic VWA1 variants; the exon 1 10-bp repeat expansion c.62_71dup, p.(Gly25ArgfsTer74), was present in 14/15 families and homozygous in 10/15.
Collective Evidence	Segregation	PMID:33559681	1.5	Segregation support included trans confirmation for compound-heterozygous cases by allele-specific PCR, Nanopore sequencing, or parental inheritance, plus an extended consanguineous family in which a homozygous VWA1 frameshift variant lay in a shared autozygous region spanning VWA1. No formal LOD score was reported.
Singular Evidence	Probands	PMID:39502942	6	Cohort study identifying biallelic VWA1 variants in affected individuals with consistent neuromuscular phenotype; includes clinical, neurophysiological, and biopsy data. 12 affected individuals had the c.62_71dup, an increase from 2 to 3 GGCGCGGAGC motifs. An additional 11 novel VWA1 variants were identified in the cohort. One familiy from this study overlaps with the previous pmid:33559681 cohort.

Experimental evidence

Total: 0.5

Per page

Category	Type	Citation	Score	Details
Function	Protein interaction	PMID:38652110	0.5	Gene-level evidence only: WARP/VWA1 is described as an extracellular-matrix protein expressed in muscle and peripheral nerve that interacts with collagen VI and perlecan; this paper did not perform a tandem-repeat/locus-specific interaction assay.

Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.