Submissions for variant NM_002473.6(MYH9):c.5074G>A (p.Ala1692Thr)

gnomAD frequency: 0.00007  dbSNP: rs767426084

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000851808	SCV000899776	uncertain significance	Macrothrombocytopenia	2019-02-01	criteria provided, single submitter	research
Illumina Laboratory Services, Illumina	RCV001150616	SCV001311697	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	RCV001150617	SCV001311698	uncertain significance	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001855731	SCV002199823	likely benign	not provided	2023-12-12	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV001150616	SCV004118807	uncertain significance	MYH9-related disorder	2022-12-20	criteria provided, single submitter	clinical testing	The MYH9 c.5074G>A variant is predicted to result in the amino acid substitution p.Ala1692Thr. This variant was reported as a variant of uncertain significance in an individual categorized as having a platelet count disorder (Supp. Table 3 TGP0566, Downes et al 2019. PubMed ID: 31064749). This variant is reported in 0.0086% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/22-36681987-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV002245650	SCV002515769	uncertain significance	Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss		no assertion criteria provided	research