Submissions for variant NM_000094.4(COL7A1):c.7349del (p.Pro2450fs)

dbSNP: rs1575425011

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001008280	SCV001168047	likely pathogenic	not provided	2018-07-26	criteria provided, single submitter	clinical testing	The c.7349delC variant in the COL7A1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant causes a frameshift starting with codon Proline 2450, changes this amino acid to a Histidine residue, and creates a premature Stop codon at position 16 of the new reading frame, denoted p.P2450HfsX16. The c.7349delC variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. This variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.7349delC as a likely pathogenic variant.
Invitae	RCV001008280	SCV004429068	pathogenic	not provided	2022-12-30	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 817173). This variant has not been reported in the literature in individuals affected with COL7A1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Pro2450Hisfs*16) in the COL7A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL7A1 are known to be pathogenic (PMID: 16971478).