ClinVar Miner

Submissions for variant NM_002474.3(MYH11):c.4706T>C (p.Met1569Thr)

gnomAD frequency: 0.00008  dbSNP: rs145074004
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000541780 SCV000641051 uncertain significance Aortic aneurysm, familial thoracic 4 2024-11-10 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1576 of the MYH11 protein (p.Met1576Thr). This variant is present in population databases (rs145074004, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with MYH11-related conditions. ClinVar contains an entry for this variant (Variation ID: 465739). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt MYH11 protein function with a negative predictive value of 95%. 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.
Ambry Genetics RCV001180820 SCV000739211 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-02-07 criteria provided, single submitter clinical testing The p.M1569T variant (also known as c.4706T>C), located in coding exon 32 of the MYH11 gene, results from a T to C substitution at nucleotide position 4706. The methionine at codon 1569 is replaced by threonine, an amino acid with similar properties, and is located in the coiled-coil domain. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV001180820 SCV001345844 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-02-09 criteria provided, single submitter clinical testing This missense variant replaces methionine with threonine at codon 1576 of the MYH11 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MYH11-related disorders in the literature. This variant has been identified in 10/282820 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001775863 SCV001474404 uncertain significance not provided 2020-08-10 criteria provided, single submitter clinical testing The MYH11 c.4706T>C; p.Met1569Thr variant (rs145074004), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 465739). This variant is only observed on ten alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. The methionine at codon 1569 is highly conserved, and computational analyses (SIFT: damaging, PolyPhen-2: benign) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the p.Met1569Thr variant is uncertain at this time.
GeneDx RCV001775863 SCV002013348 uncertain significance not provided 2022-10-26 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Fulgent Genetics, Fulgent Genetics RCV002497127 SCV002806754 uncertain significance Aortic aneurysm, familial thoracic 4; Visceral myopathy 2; Megacystis-microcolon-intestinal hypoperistalsis syndrome 2 2021-10-28 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV001775863 SCV003817168 uncertain significance not provided 2020-10-06 criteria provided, single submitter clinical testing

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