Submissions for variant NM_002473.6(MYH9):c.2635A>C (p.Met879Leu)

gnomAD frequency: 0.00005  dbSNP: rs200328859

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000151342	SCV000199316	likely benign	not specified	2013-06-12	criteria provided, single submitter	clinical testing	The Met879Leu in Exon 22 of MYH9: This variant is not expected to have clinical significance due to a lack of conservation across species, including mammals. Of note, cow, lizard and puffer fish have a leucine (Leu) at this position despite high nearby amino acid conservation. In addition, computational analyses (PolyP hen2, SIFT, AlignGVGD) do not suggest a high likelihood of impact to the protein . This variant has been identified in 1/8600 of European American chromosomes by the NHLBI Exome Sequencing Project and in 1% (2/200) Chinese chromosomes by the 1000 Genomes Project (http://evs.gs.washington.edu/EVS/; dbSNP rs200328859).
Illumina Laboratory Services, Illumina	RCV000306348	SCV000438412	likely benign	Autosomal dominant nonsyndromic hearing loss 17	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	RCV000344830	SCV000438413	benign	MYH9-related disorder	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae	RCV001850063	SCV002230145	likely benign	not provided	2023-11-17	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003927456	SCV004741556	likely benign	MYH9-related condition	2020-03-02	criteria provided, single submitter	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).