ClinVar Miner

Submissions for variant NM_000094.3(COL7A1):c.3942dup (p.Asn1315fs) (rs747912732)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000274389 SCV000329315 pathogenic not provided 2017-08-01 criteria provided, single submitter clinical testing The c.3942dupG pathogenic variant in the COL7A1 gene has been reported previously in association with RDEB (Varki et al., 2007 (3943insG)). The c.3942dupG variant causes a frameshift starting with codon Asn1315, changes this amino acid to a Glutamine residue, and creates a premature Stop codon at position 45 of the new reading frame, denoted p.Asn1315GlufsX45. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.3942dupG variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.3942dupG as a pathogenic variant.
Illumina Clinical Services Laboratory,Illumina RCV000778707 SCV000915060 likely pathogenic Dystrophic epidermolysis bullosa 2018-12-18 criteria provided, single submitter clinical testing The COL7A1 c.3942dupG (p.Asn1315GlufsTer45) frameshift variant, also referred to as 3943insG, has been reported in one study and is found in a total of three individuals, including in two in a compound heterozygous state and in one in a heterozygous state in whom a second variant was not identified (Varki et al. 2007). The inheritance pattern and clinical phenotypes of the three individuals were consistent with autosomal recessive dystrophic epidermolysis bullosa. Control data are unavailable for this variant, which is reported at a frequency of 0.000413 in the Ashkenazi Jewish population of the Genome Aggregation Database. Based on the evidence and due to the potential impact of frameshift variants, the p.Asn1315GlufsTer45 variant is classified as likely pathogenic for dystrophic epidermolysis bullosa. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000274389 SCV000956453 pathogenic not provided 2020-08-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn1315Glufs*45) in the COL7A1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs747912732, ExAC 0.002%). This variant has been observed in individuals affected with dystrophic epidermolysis bullosa (PMID: 16971478). ClinVar contains an entry for this variant (Variation ID: 279787). Loss-of-function variants in COL7A1 are known to be pathogenic (PMID: 16971478). For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000274389 SCV001153945 uncertain significance not provided 2017-01-01 criteria provided, single submitter clinical testing

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