ClinVar Miner

Submissions for variant NM_001849.4(COL6A2):c.1402C>T (p.Arg468Ter)

gnomAD frequency: 0.00001  dbSNP: rs374669775
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000685322 SCV000812800 pathogenic Bethlem myopathy 1A 2025-01-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg468*) in the COL6A2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL6A2 are known to be pathogenic (PMID: 19884007, 20976770). This variant is present in population databases (rs374669775, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with autosomal recessive collagenopathy (PMID: 23326386, 29419890). ClinVar contains an entry for this variant (Variation ID: 565700). For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV001311585 SCV001501819 pathogenic not provided 2020-07-01 criteria provided, single submitter clinical testing
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre RCV003989581 SCV004806453 uncertain significance Ullrich congenital muscular dystrophy 1B 2024-03-25 criteria provided, single submitter clinical testing
Neurogenomics Lab, Neuroscience Institute, University Of Cape Town RCV005091997 SCV005849065 pathogenic Collagen 6-related myopathy 2025-02-10 criteria provided, single submitter research PM2_supporting: the highest population allele frequency in gnomAD v2.1.1 is 0.0001001 (0.01%; 1/9990 alleles in Ashkenazi Jewish population) and the variant is absent from gnomAD v3.1.2 (adequate coverage >20X confirmed). The variant is absent from an internal database. PM1 met: this variant is in the collagen triple helix (TH) repeat domain together with other pathogenic variants (PMID 24038877). PS4_moderate: variant identified in at least 5 unrelated probands with consistent phenotype for disorder (PMID 23326386, 20976770, 37569848, 29419890). PVS1 met: null variant (nonsense, predicted to undergo NMD, exon is present in a biologically-relevant transcript in a gene where LOF is a known mechanism of disease). Sequencing funded by the International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD): https://www.ucl.ac.uk/genomic-medicine-neuromuscular-diseases/.
GeneReviews RCV000685322 SCV001519045 not provided Bethlem myopathy 1A no assertion provided literature only Common variant that in homozygosity results in loss of function

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