Submissions for variant NM_002473.6(MYH9):c.3320G>A (p.Arg1107Gln)

gnomAD frequency: 0.00004  dbSNP: rs137924205

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000324164	SCV000438398	benign	MYH9-related disorder	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000360226	SCV000438399	likely benign	Autosomal dominant nonsyndromic hearing loss 17	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV001449723	SCV001652988	benign	not specified	2020-09-04	criteria provided, single submitter	clinical testing	The p.Arg1107Gln variant in MYH9 is classified as benign because it has been identified in 0.2% (75/34538) of Latino chromosomes by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BA1.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002057800	SCV002341656	likely benign	not provided	2023-12-18	criteria provided, single submitter	clinical testing
GeneDx	RCV002057800	SCV002540543	uncertain significance	not provided	2024-05-07	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign in association with MYH9-related disorders to our knowledge; This variant is associated with the following publications: (PMID: 27527345)
Revvity Omics, Revvity	RCV002057800	SCV003817777	uncertain significance	not provided	2020-11-10	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000324164	SCV004764481	likely benign	MYH9-related disorder	2023-12-11	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).