ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.5704G>C (p.Glu1902Gln) (rs187073962)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000242151 SCV000318634 uncertain significance Cardiovascular phenotype 2013-05-11 criteria provided, single submitter clinical testing
ClinGen Inherited Cardiomyopathy Variant Curation Expert Panel, RCV000758073 SCV000564461 uncertain significance Cardiomyopathy 2016-12-15 reviewed by expert panel curation The c.5704G>C (p.Glu1902Gln) variant in MYH7 has been reported in 5 individuals with hypertrophic cardiomyopathy (PMID:27532257; PMID:25086479; Partners LMM ClinVar SCV000059629.5; SHaRe consortium, PMID: 30297972) but has also been identified in 0.1% (9/8654) of East Asian chromosomes by ExAC (http://exac.broadinstitute.org). Since the MYH7 specifications state that PS4 is only applicable if a variant is absent or rare in large population studies, PS4 criterion was not applied (PMID:29300372). In summary, due to lack of evidence, this variant meets criteria to be classified as uncertain significance for cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (PMID:29300372): No criteria applied.
Illumina Clinical Services Laboratory,Illumina RCV000263236 SCV000385870 likely benign Hypertrophic cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000331432 SCV000385871 likely benign Left ventricular noncompaction cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000369831 SCV000385872 likely benign Dilated Cardiomyopathy, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000277557 SCV000385873 likely benign Scapuloperoneal myopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000325552 SCV000385874 likely benign Myopathy, distal, 1 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000382622 SCV000385875 likely benign Myosin storage myopathy 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000263236 SCV000623750 likely benign Hypertrophic cardiomyopathy 2017-10-16 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000035977 SCV000059629 uncertain significance not specified 2016-02-05 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
Stanford Center for Inherited Cardiovascular Disease,Stanford University RCV000035977 SCV000280371 uncertain significance not specified no assertion criteria provided clinical testing Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. p.Glu1902Gln (p.E1902Q; c.5704G>C) in MYH7. This variant is novel. This variant results in glutamate at codon 1902 replaced by glutamine, an amino acid with similar properties. In silico analysis with PolyPhen-2 predicts the variant to be possibly damaging, but tolerated by SIFT. Mutation Taster predicts this variant to be disease causing. The glutamate at codon 1902 is conserved across species, as are neighboring amino acids. No other variants have been reported in association with disease at this codon and nearby codons. In total the variant has not been seen in ~6,000 published controls and individuals from publicly available population datasets. There is no variation at codon 1902 listed in the NHLBI Exome Sequencing Project dataset, which currently includes variant calls on ~6,000 Caucasian and African American individuals (as of 5/15/13). Note that this dataset does not match the patient's ancestry (FIlipino). Based on data from the 1000 genomes project, the C-allele has an overal frequency of approximately 0.09% (2/2189). This amino acid position is well conserved on sequence alignment. The observed C-allele occurred in the Japanese population at a frequency of 1.12% (2/179).

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