Submissions for variant NM_001845.6(COL4A1):c.3946C>G (p.Gln1316Glu)

gnomAD frequency: 0.00020  dbSNP: rs377122126

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001721546	SCV000564900	likely benign	not provided	2021-06-01	criteria provided, single submitter	clinical testing	Identified in a patient with muscle-brain-eye disease in published literature, but the variant was also present in her unaffected father (Labelle-Dumais et al., 2011); Identified in a patient with status epilepticus, developmental delay, and hypotonia in published literature, but familial segregation information was not provided (Hesse et al., 2018); This variant is associated with the following publications: (PMID: 21625620, 29778030, 27535533, 31996268)
Illumina Laboratory Services, Illumina	RCV002248697	SCV001272626	benign	Brain small vessel disease 1 with or without ocular anomalies	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV001114723	SCV001272627	benign	Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001721546	SCV002395320	likely benign	not provided	2024-12-31	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001721546	SCV002497685	likely benign	not provided	2024-11-01	criteria provided, single submitter	clinical testing	COL4A1: BS2
PreventionGenetics, part of Exact Sciences	RCV004535495	SCV004120040	uncertain significance	COL4A1-related disorder	2024-03-27	no assertion criteria provided	clinical testing	The COL4A1 c.3946C>G variant is predicted to result in the amino acid substitution p.Gln1316Glu. This variant was reported in an individual with congenital muscular dystrophy with ocular and cerebral involvement and was also present in the patient’s father (Labelle-Dumais et al 2011. PubMed ID: 21625620). This variant was also reported as likely pathogenic in an individual with status epilepticus, development delay, hypotonia, and sleep disturbances (Patient 38, Hesse et al 2018. PubMed ID: 29778030). This variant was also identified in a study of individuals with dementia with Lewy bodies (Supplementary Table 3, Orme et al 2020. PubMed ID: 31996268). This variant is reported in 0.023% of alleles in individuals of European (Non-Finnish) descent in gnomAD, which may be too common to be causative. This variant is interpreted as benign and likely benign in the ClinVar database by multiple laboratories (https://www.ncbi.nlm.nih.gov/clinvar/variation/418141). Although we suspect this variant may be benign, at this time, the clinical significance is uncertain due to the absence of conclusive functional and genetic evidence.