ClinVar Miner

Submissions for variant NM_053025.4(MYLK):c.619G>A (p.Val207Met)

gnomAD frequency: 0.00003  dbSNP: rs756560698
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000249352 SCV000320433 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2015-11-13 criteria provided, single submitter clinical testing The p.V207M variant (also known as c.619G>A), located in coding exon 5 of the MYLK gene, results from a G to A substitution at nucleotide position 619. The valine at codon 207 is replaced by methionine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is not well conserved in available vertebrate species. 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 variant remains unclear.
Illumina Laboratory Services, Illumina RCV000249352 SCV000440339 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000520122 SCV000620487 uncertain significance not provided 2020-04-23 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; Reported in ClinVar (ClinVar Variant ID# 264468; Landrum et al., 2016)
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000659934 SCV000781838 likely benign Connective tissue disorder 2016-11-01 criteria provided, single submitter clinical testing
Invitae RCV001045808 SCV001209682 uncertain significance Aortic aneurysm, familial thoracic 7 2024-01-27 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 207 of the MYLK protein (p.Val207Met). This variant is present in population databases (rs756560698, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of MYLK-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 264468). 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 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.

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