ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.4844_4846AGA[2] (p.Lys1617del) (rs121913648)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000526457 SCV000623724 pathogenic Hypertrophic cardiomyopathy 2019-11-06 criteria provided, single submitter clinical testing This variant, c.4850_4852delAGA, results in the deletion of 1 amino acid of the MYH7 protein (p.Lys1617del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several families and individuals affected with early-onset Laing distal myopathy (PMID: 24300783, 15322983, 27387980, 16103042, 24664454). ClinVar contains an entry for this variant (Variation ID: 190401). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acids is currently unknown. For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics,Klinikum rechts der Isar RCV000192202 SCV000680307 pathogenic Myopathy, distal, 1 2017-10-18 criteria provided, single submitter clinical testing
GeneDx RCV000599460 SCV000709903 pathogenic not provided 2018-10-04 criteria provided, single submitter clinical testing The c.4850_4852delAGA variant has been reported previously in association with Laing distal myopathy and other MYH7-related disorders (Meredith et al., 2004; Komlósi et al., 2014; Lamont et al., 2014; Oda et al., 2015; Fiorilloet al., 2016). The c.4850_4852delAGA variant results in an in-frame deletion of 1 amino acid residue, denoted p.Lys1617del. This variant is not observed in large population cohorts (Lek et al., 2016). Additionally, in-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Furthermore,in-frame deletions have been reported in the Human Gene Mutation Database in association with MYH7-related disorders (Stenson et al., 2014). Therefore, the c.4850_4852delAGA variant is considered a pathogenic variant and its presence is consistent with the diagnosis of an MYH7-related disorder in this individual.
OMIM RCV000192202 SCV000035430 pathogenic Myopathy, distal, 1 2004-10-01 no assertion criteria provided literature only
Neurogenetics Laboratory,Royal Perth Hospital RCV000192202 SCV000119904 pathogenic Myopathy, distal, 1 2013-01-01 no assertion criteria provided clinical testing
GeneReviews RCV000192202 SCV000223108 pathogenic Myopathy, distal, 1 2015-03-12 no assertion criteria provided literature only

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