ClinVar Miner

Submissions for variant NM_002474.3(MYH11):c.4993C>T (p.Arg1665Cys)

gnomAD frequency: 0.00002  dbSNP: rs768569707
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000475772 SCV000543730 uncertain significance Aortic aneurysm, familial thoracic 4 2023-09-29 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MYH11 protein function. ClinVar contains an entry for this variant (Variation ID: 405480). This missense change has been observed in individual(s) with left ventricular noncompaction (PMID: 32600061). This variant is present in population databases (rs768569707, gnomAD 0.009%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1672 of the MYH11 protein (p.Arg1672Cys).
GeneDx RCV000523310 SCV000620194 uncertain significance not provided 2019-08-20 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Reported in ClinVar but additional evidence is not available (ClinVar Variant ID# 405480; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 32600061)
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000769659 SCV000901067 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2019-12-23 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000769659 SCV001340900 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-04-26 criteria provided, single submitter clinical testing This missense variant replaces arginine with cysteine at codon 1672 of the MYH11 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with left ventricular noncompaction (PMID: 32600061). This variant has been identified in 13/251482 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
All of Us Research Program, National Institutes of Health RCV000769659 SCV004821152 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-11-28 criteria provided, single submitter clinical testing This missense variant replaces arginine with cysteine at codon 1672 of the MYH11 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with left ventricular noncompaction (PMID: 32600061). This variant has been identified in 13/251482 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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