Submissions for variant NM_001845.6(COL4A1):c.1807C>T (p.Pro603Ser)

gnomAD frequency: 0.00002  dbSNP: rs747585517

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000625809	SCV000746366	likely pathogenic	Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome	2017-12-03	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001529466	SCV002205905	uncertain significance	not provided	2025-01-08	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 603 of the COL4A1 protein (p.Pro603Ser). This variant is present in population databases (rs747585517, gnomAD 0.002%). This missense change has been observed in individual(s) with multi-cystic dysplastic kidney (PMID: 31230195). ClinVar contains an entry for this variant (Variation ID: 522668). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt COL4A1 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics	RCV005004277	SCV005632426	uncertain significance	Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome; Brain small vessel disease 1 with or without ocular anomalies; Hemorrhage, intracerebral, susceptibility to; Retinal arterial tortuosity; Microangiopathy and leukoencephalopathy, pontine, autosomal dominant	2023-12-28	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529466	SCV001742977	uncertain significance	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001529466	SCV001808406	uncertain significance	not provided		no assertion criteria provided	clinical testing
Yale Center for Mendelian Genomics, Yale University	RCV001849420	SCV002106634	likely pathogenic	Congenital anomaly of kidney and urinary tract	2019-06-22	no assertion criteria provided	literature only