Submissions for variant NM_000092.4(COL4A4):c.50A>G (p.Lys17Arg) (rs114969026)

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000480643	SCV000570551	uncertain significance	not specified	2016-06-02	criteria provided, single submitter	clinical testing	The K17R variant in the COL4A4 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. While not present in the homozygous state, the NHLBI ESP Exome Sequencing Project reports K17R was observed in 46/3854 (1.19%) alleles from individuals of African American background, indicating it may be a rare variant in this population. The K17R variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved, and in silico analysis predicts this variant likely does not alter the protein structure/function. We interpret K17R as a variant of uncertain significance.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine	RCV000480643	SCV000966410	likely benign	not specified	2016-03-21	criteria provided, single submitter	clinical testing	p.Lys17Arg in exon 2 of COL4A4: This variant is not expected to have clinical si gnificance because it has been identified in 1.13% (111/9798) of African chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs114969026).
Invitae	RCV000904082	SCV001048583	benign	not provided	2019-12-31	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000904082	SCV001143242	benign	not provided	2019-06-24	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV001138181	SCV001298214	likely benign	Alport syndrome	2018-01-13	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.