Submissions for variant NM_001845.6(COL4A1):c.2201C>G (p.Pro734Arg)

gnomAD frequency: 0.00001  dbSNP: rs527530568

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Fulgent Genetics, Fulgent Genetics	RCV002489838	SCV002778716	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	2021-10-22	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001795740	SCV003246974	uncertain significance	not provided	2024-10-10	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 734 of the COL4A1 protein (p.Pro734Arg). This variant is present in population databases (rs527530568, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with COL4A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1328308). 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.
CeGaT Center for Human Genetics Tuebingen	RCV001795740	SCV004135607	uncertain significance	not provided	2023-10-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001795740	SCV005331670	uncertain significance	not provided	2024-03-28	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; 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
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001795740	SCV002035437	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001795740	SCV002037396	uncertain significance	not provided		no assertion criteria provided	clinical testing