Submissions for variant NM_000213.5(ITGB4):c.2929C>T (p.Arg977Cys)

gnomAD frequency: 0.00214  dbSNP: rs145976111

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000261826	SCV000406561	likely benign	Junctional epidermolysis bullosa with pyloric atresia	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Invitae	RCV000950475	SCV001096786	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000950475	SCV001151420	likely benign	not provided	2020-02-01	criteria provided, single submitter	clinical testing
Johns Hopkins Genomics, Johns Hopkins University	RCV000261826	SCV001438380	benign	Junctional epidermolysis bullosa with pyloric atresia	2020-09-23	criteria provided, single submitter	clinical testing
GeneDx	RCV000950475	SCV001820560	likely benign	not provided	2020-09-18	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 29526452)
Sydney Genome Diagnostics, Children's Hospital Westmead	RCV001328148	SCV001449345	uncertain significance	Nephrotic syndrome	2018-10-24	no assertion criteria provided	clinical testing	This patient is heterozygous for a variant of unknown clinical significance (VOUS), c.2929C>T (p.Arg977Cys), in the ITGB4 gene. To our knowledge, this variant has not been previously reported in the literature to be associated with disease. It has been listed in Exome Aggregation Consortium (ExAC) with a frequency of 335 out of 117600 alleles (0.2%). p.Arg977, is a highly conserved amino acid (up to 11 species) and there is also a large physicochemical difference between the wild type arginine and mutant cysteine. In silico analysis (Alamut Visual v2.6) using Align GVGD, PolyPhen2, SIFT and Mutation Taster all suggest that this variant is likely to be pathogenic.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001729538	SCV001977865	benign	not specified		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000950475	SCV001978568	likely benign	not provided		no assertion criteria provided	clinical testing
Narges Medical Genetic and Prenatal Diagnosis Lab	RCV003327395	SCV004035005	benign	Epidermolysis bullosa, junctional 5A, intermediate		no assertion criteria provided	clinical testing