Submissions for variant NM_001845.6(COL4A1):c.2624C>G (p.Pro875Arg)

gnomAD frequency: 0.00055  dbSNP: rs201964644

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV002248569	SCV000382436	benign	Brain small vessel disease 1 with or without ocular anomalies	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000363989	SCV000382437	benign	Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000276504	SCV000382438	likely benign	Porencephalic cyst	2016-06-14	criteria provided, single submitter	clinical testing
Invitae	RCV000904627	SCV001049151	likely benign	not provided	2024-01-25	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000904627	SCV001149085	likely benign	not provided	2023-06-01	criteria provided, single submitter	clinical testing	COL4A1: BS1
GeneDx	RCV000904627	SCV002098166	uncertain significance	not provided	2023-05-04	criteria provided, single submitter	clinical testing	Reported in one family with chronic intestinal pseudo-obstruction (Dong et al., 2019); however, additional clinical information was not provided; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Occurs in the triple helical domain at the Y position in the canonical Gly-X-Y repeat; although this variant may have an effect on normal protein folding and function, missense substitution at the Y position is not a common mechanism of disease (HGMD); This variant is associated with the following publications: (PMID: 31389005)
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000904627	SCV002035086	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000904627	SCV002037900	likely benign	not provided		no assertion criteria provided	clinical testing