Submissions for variant NM_000094.4(COL7A1):c.3942dup (p.Asn1315fs)

dbSNP: rs747912732

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000274389	SCV000329315	pathogenic	not provided	2022-05-31	criteria provided, single submitter	clinical testing	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; This variant is associated with the following publications: (PMID: 16971478, 29625052)
Illumina Laboratory Services, Illumina	RCV000778707	SCV000915060	likely pathogenic	Epidermolysis bullosa dystrophica	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000274389	SCV000956453	pathogenic	not provided	2024-01-04	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. Loss-of-function variants in COL7A1 are known to be pathogenic (PMID: 16971478). This variant is present in population databases (rs747912732, gnomAD 0.04%). This premature translational stop signal has been observed in individuals with autosomal recessive dystrophic epidermolysis bullosa (PMID: 16971478). ClinVar contains an entry for this variant (Variation ID: 279787). For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV000274389	SCV001153945	uncertain significance	not provided	2017-01-01	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000778707	SCV002079259	pathogenic	Epidermolysis bullosa dystrophica	2020-08-03	no assertion criteria provided	clinical testing