Submissions for variant NM_001845.6(COL4A1):c.329T>C (p.Ile110Thr)

gnomAD frequency: 0.00021  dbSNP: rs138269346

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000329791	SCV000382562	likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV002248598	SCV000382563	likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV000275704	SCV000382564	likely benign	Porencephalic cyst	2016-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001557741	SCV001779558	uncertain significance	not provided	2024-09-30	criteria provided, single submitter	clinical testing	Reported in an individual with Marfan syndrome who also harbors a de novo pathogenic variant in the FBN1 gene (PMID: 30087447) and reported in association with intracerebral hemorrhage (PMID: 34031201); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 34031201, 35711275, 34220303, 30087447)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001557741	SCV002483557	likely benign	not provided	2024-12-17	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002522266	SCV003688748	likely benign	Inborn genetic diseases	2021-08-26	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Revvity Omics, Revvity	RCV001557741	SCV003828169	uncertain significance	not provided	2023-04-26	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001557741	SCV004135626	uncertain significance	not provided	2022-10-01	criteria provided, single submitter	clinical testing	COL4A1: PP3
PreventionGenetics, part of Exact Sciences	RCV004739679	SCV005343838	likely benign	COL4A1-related disorder	2024-03-28	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).