Submissions for variant NM_053025.4(MYLK):c.5120G>A (p.Arg1707His)

dbSNP: rs1328179065

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000531919	SCV000650559	uncertain significance	Aortic aneurysm, familial thoracic 7	2023-05-01	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 MYLK protein function. ClinVar contains an entry for this variant (Variation ID: 471733). This variant has not been reported in the literature in individuals affected with MYLK-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1707 of the MYLK protein (p.Arg1707His).
GeneDx	RCV001755871	SCV002006550	uncertain significance	not provided	2020-08-14	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798894	SCV002043676	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2020-06-05	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001798894	SCV002642234	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2020-08-17	criteria provided, single submitter	clinical testing	The p.R1707H variant (also known as c.5120G>A), located in coding exon 28 of the MYLK gene, results from a G to A substitution at nucleotide position 5120. The arginine at codon 1707 is replaced by histidine, an amino acid with highly similar properties. 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.