ClinVar Miner

Submissions for variant NM_003803.4(MYOM1):c.3190C>T (p.His1064Tyr) (rs755409090)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000208137 SCV000264115 uncertain significance Sudden cardiac death 2015-10-29 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000613984 SCV000731706 likely benign not specified 2017-06-27 criteria provided, single submitter clinical testing p.His1064Tyr in exon 21 of MYOM1: This variant is not expected to have clinical significance due to a lack of conservation across species, including mammals. Of note, histidine (His) at position 1064 is not conserved in mammals or evolution arily distant species, and 39 species carry a tyrosine (Tyr), supporting that th is change may be tolerated. This variant has been identified in 3/25290 of Finni sh chromosomes by the genome Aggregation Database (gnomAD, http://gnomad.broadin stitute.org; dbSNP rs75540909), and has been reported in ClinVar (Variation ID# 222744).
Invitae RCV001068752 SCV001233883 uncertain significance Hypertrophic cardiomyopathy 2020-01-13 criteria provided, single submitter clinical testing This sequence change replaces histidine with tyrosine at codon 1064 of the MYOM1 protein (p.His1064Tyr). The histidine residue is weakly conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is present in population databases (rs755409090, ExAC 0.002%). This variant has not been reported in the literature in individuals with MYOM1-related conditions. ClinVar contains an entry for this variant (Variation ID: 222744). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The tyrosine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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