ClinVar Miner

Submissions for variant NM_053025.4(MYLK):c.4130C>T (p.Thr1377Met)

gnomAD frequency: 0.00003  dbSNP: rs750002545
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000576566 SCV000678227 uncertain significance Aortic aneurysm, familial thoracic 7 2017-08-01 criteria provided, single submitter clinical testing MYLK NM_053026 exon23 p.Thr1308Met (c.3923C>T): This variant has not been reported in the literature but is present in 2/34220 Latino chromosomes in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs750002545). This variant methonine (Met) is present in >10 species including mammals, and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
GeneDx RCV001764694 SCV002008365 uncertain significance not provided 2019-05-06 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance but additional evidence is not available (ClinVar Variant ID# 487468; Landrum et al., 2016); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function
Ambry Genetics RCV002330993 SCV002628553 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2022-03-16 criteria provided, single submitter clinical testing The p.T1377M variant (also known as c.4130C>T), located in coding exon 21 of the MYLK gene, results from a C to T substitution at nucleotide position 4130. The threonine at codon 1377 is replaced by methionine, an amino acid with similar properties. This amino acid position is poorly 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV003224340 SCV003920249 uncertain significance Aortic aneurysm, familial thoracic 7; Megacystis-microcolon-intestinal hypoperistalsis syndrome 1 2021-03-30 criteria provided, single submitter clinical testing MYLK NM_053026 exon23 p.Thr1308Met (c.3923C>T): This variant has not been reported in the literature but is present in 2/34220 Latino chromosomes in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs750002545). This variant methonine (Met) is present in >10 species including mammals, and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

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