ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.4078G>A (p.Val1360Ile) (rs373231077)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000035885 SCV000059536 uncertain significance not specified 2019-08-12 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Val1360Ile variant in MYH7 has been identified in 4 individuals with HCM (Wang 2014, Homburger 2016, LMM data). It has also been identified in 8/129146 European chromosomes by gnomAD and reported in ClinVar (Variation ID #42991). Computational prediction tools and conservation analyses suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: BP4.
Invitae RCV001062732 SCV001227549 uncertain significance Hypertrophic cardiomyopathy 2019-12-04 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 1360 of the MYH7 protein (p.Val1360Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs373231077, ExAC 0.01%). This variant has been observed in individuals affected with hypertrophic cardiomyopathy (PMID: 25132132, 27247418, 27532257). ClinVar contains an entry for this variant (Variation ID: 42991). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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.
Color RCV001188109 SCV001355081 uncertain significance Cardiomyopathy 2019-09-23 criteria provided, single submitter clinical testing
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000035885 SCV000280346 uncertain significance not specified 2014-01-31 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.Val1360Ile (c.4078G>A) in MYH7 This is a novel variant. We classify it as a variant of uncertain significance This variant has not been described in published literature to date (as of October 2nd, 2012). Conservation analysis indicates that Valine is not highly conserved at position 1360 across species and isoforms. In total the variant has been seen in 1/6577 published controls and publicly available population datasets. The variant was recently reported online in 1 of ~4300 Caucasian individuals and 0 of 2203 African-American individuals in the NHLBI Exome Sequencing Project dataset (as of October 2nd, 2012). The phenotype of that individuals is not publicly available, however the cohorts that were merged to create this dataset were all either general population samples or samples recruited for common cardiovascular disease such as hypertension. Note that other very likely disease causing sarcomere variants have been seen in this sample at this frequency. GeneDx reports the variant is absent in 274 presumably healthy individuals.

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