Submissions for variant NM_000092.5(COL4A4):c.2690G>A (p.Gly897Glu)

gnomAD frequency: 0.00001  dbSNP: rs121912860

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000666567	SCV000790877	likely pathogenic	Autosomal recessive Alport syndrome	2017-04-12	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000710841	SCV000841146	pathogenic	not provided	2018-06-20	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000710841	SCV001236856	pathogenic	not provided	2024-06-26	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 897 of the COL4A4 protein (p.Gly897Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of Alport syndrome (PMID: 8787673, 26809805). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 17406). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt COL4A4 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000018949	SCV001370024	likely pathogenic	Benign familial hematuria	2018-12-10	criteria provided, single submitter	clinical testing	This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM2,PP3.
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV000018949	SCV002765003	likely pathogenic	Benign familial hematuria	2022-03-14	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV005003386	SCV002807505	pathogenic	Autosomal recessive Alport syndrome; Hematuria, benign familial, 1	2024-03-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000710841	SCV005081038	pathogenic	not provided	2024-01-25	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Affects a glycine residue in a Gly-X-Y motif in the triple helical region of the COL4A4 gene, where the majority of pathogenic missense variants occur, and is predicted to disrupt normal protein folding and function (PMID: 10752524, 24077912); This variant is associated with the following publications: (PMID: 10074584, 8787673, 11961012, 15280517, 10460935, 31589614, 10752524, 24077912, 26809805, 14582039)
OMIM	RCV004576907	SCV000039236	pathogenic	Hematuria, benign familial, 1	1996-09-01	no assertion criteria provided	literature only
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000710841	SCV001928919	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000710841	SCV001956583	pathogenic	not provided		no assertion criteria provided	clinical testing