Submissions for variant NM_002474.3(MYH11):c.5767G>A (p.Ala1923Thr)

gnomAD frequency: 0.00004  dbSNP: rs571504063

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000756379	SCV000234885	uncertain significance	not provided	2023-11-06	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 21529752)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000756379	SCV000884174	uncertain significance	not provided	2017-07-04	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000796819	SCV000936347	uncertain significance	Aortic aneurysm, familial thoracic 4	2022-10-23	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1930 of the MYH11 protein (p.Ala1930Thr). This variant is present in population databases (rs571504063, gnomAD 0.03%). 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: 201092). 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. 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 Diagnostics, LLC DBA Color Health	RCV001186485	SCV001352921	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2023-11-22	criteria provided, single submitter	clinical testing	This missense variant replaces alanine with threonine at codon 1930 of the MYH11 protein. Computational prediction tool indicates that this variant may have a neutral impact on protein structure and function. 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 19/250374 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.
Ambry Genetics	RCV001186485	SCV002651308	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2021-12-08	criteria provided, single submitter	clinical testing	The p.A1923T variant (also known as c.5767G>A), located in coding exon 39 of the MYH11 gene, results from a G to A substitution at nucleotide position 5767. The alanine at codon 1923 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV002485203	SCV002787317	uncertain significance	Aortic aneurysm, familial thoracic 4; Visceral myopathy 2; Megacystis-microcolon-intestinal hypoperistalsis syndrome 2	2022-05-09	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001186485	SCV003837930	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2022-05-19	criteria provided, single submitter	clinical testing