Submissions for variant NM_004370.6(COL12A1):c.4738del (p.Ser1580fs)

gnomAD frequency: 0.00002  dbSNP: rs1471550984

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000813936	SCV000954320	pathogenic	Ullrich congenital muscular dystrophy 2; Bethlem myopathy 2	2024-12-15	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser1580Alafs*3) in the COL12A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL12A1 are known to be pathogenic (PMID: 24334604, 28973083). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with COL12A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 657345). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV004820121	SCV005440852	likely pathogenic	not provided	2024-06-24	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease