ClinVar Miner

Submissions for variant NM_053025.4(MYLK):c.1724C>T (p.Pro575Leu)

gnomAD frequency: 0.00003  dbSNP: rs761639849
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000472490 SCV000550025 uncertain significance Aortic aneurysm, familial thoracic 7 2023-11-20 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 575 of the MYLK protein (p.Pro575Leu). This variant is present in population databases (rs761639849, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with MYLK-related conditions. ClinVar contains an entry for this variant (Variation ID: 409697). 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 80%. 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000472490 SCV000898845 uncertain significance Aortic aneurysm, familial thoracic 7 2018-11-30 criteria provided, single submitter clinical testing MYLK NM_053025.3 exon 13 p.Pro575Leu (c.1724C>T): This variant has not been reported in the literature but it is present in 0.01% (4/23476) of South Asian alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/3-123441055-G-A). This variant is present in ClinVar (Variation ID:409697). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
GeneDx RCV001561533 SCV001784158 uncertain significance not provided 2022-03-17 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
Ambry Genetics RCV002402275 SCV002712473 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2018-10-04 criteria provided, single submitter clinical testing The p.P575L variant (also known as c.1724C>T), located in coding exon 10 of the MYLK gene, results from a C to T substitution at nucleotide position 1724. The proline at codon 575 is replaced by leucine, an amino acid with similar properties. This amino acid position is highly 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 alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002489059 SCV002787318 uncertain significance Aortic aneurysm, familial thoracic 7; Megacystis-microcolon-intestinal hypoperistalsis syndrome 1 2021-07-22 criteria provided, single submitter clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV002489059 SCV003920255 uncertain significance Aortic aneurysm, familial thoracic 7; Megacystis-microcolon-intestinal hypoperistalsis syndrome 1 2021-03-30 criteria provided, single submitter clinical testing MYLK NM_053025.3 exon 13 p.Pro575Leu (c.1724C>T): This variant has not been reported in the literature but it is present in 0.01% (4/23476) of South Asian alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/3-123441055-G-A). This variant is present in ClinVar (Variation ID:409697). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

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