ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.4321G>T (p.Ala1441Ser) (rs745414245)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Agnes Ginges Centre for Molecular Cardiology,Centenary Institute RCV000201892 SCV000256651 uncertain significance Sudden unexplained death 2015-05-01 criteria provided, single submitter research The MYH7 Ala1441Ser variant is located within the myosin tail region of the MYH7 gene and is observed as a singleton event in the ExAC population database (http://exac.broadinstitute.org/), with a minor allele frequency of 0.000008239. We detected this rare variant in a sudden unexplained death case, with no signs of cardiomyopathy found on autopsy. The alanine (Ala) at position 1441 is highly conserved across multiple species and multiple in silico models predict this variant to impact on normal protein function (SIFT: deleterious, MutationTaster: disease-causing, PolyPhen2: possibly damaging). No reports of this variant was found in the literature. Further evidence is required to understand the role of this variant in disease or normal variation. Thus, we classify this variant as of "unknown significance".
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000172044 SCV000054825 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
Color RCV000777701 SCV000913640 uncertain significance Cardiomyopathy 2018-04-26 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the LMM domain of the MYH7 protein, a C-terminal tail region that forms the thick filament backbone and interacts with other proteins. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein function. Computational splicing tools suggest that this variant may not impact the RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has the variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 6/277166 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
Illumina Clinical Services Laboratory,Illumina RCV000339453 SCV000385963 uncertain significance Myosin storage myopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000384692 SCV000385964 uncertain significance Dilated Cardiomyopathy, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000290332 SCV000385965 uncertain significance Left ventricular noncompaction cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000345240 SCV000385966 uncertain significance Hypertrophic cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000390901 SCV000385967 uncertain significance Scapuloperoneal myopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000313875 SCV000385968 uncertain significance Myopathy, distal, 1 2016-06-14 criteria provided, single submitter clinical testing

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