ClinVar Miner

Submissions for variant NM_053025.4(MYLK):c.3577A>C (p.Ser1193Arg)

gnomAD frequency: 0.00002  dbSNP: rs759317891
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000807639 SCV000947704 uncertain significance Aortic aneurysm, familial thoracic 7 2021-08-30 criteria provided, single submitter clinical testing This sequence change replaces serine with arginine at codon 1193 of the MYLK protein (p.Ser1193Arg). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and arginine. This variant is present in population databases (rs759317891, ExAC 0.007%). This variant has not been reported in the literature in individuals affected with MYLK-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
GeneDx RCV001551778 SCV001772354 uncertain significance not provided 2020-11-26 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Reported in ClinVar as a variant of clinical significance (ClinVar Variant ID# 652142; Landrum et al., 2016)
Ambry Genetics RCV002453814 SCV002615643 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2022-08-16 criteria provided, single submitter clinical testing The p.S1193R variant (also known as c.3577A>C), located in coding exon 17 of the MYLK gene, results from an A to C substitution at nucleotide position 3577. The serine at codon 1193 is replaced by arginine, an amino acid with dissimilar 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 RCV002501091 SCV002788833 uncertain significance Aortic aneurysm, familial thoracic 7; Megacystis-microcolon-intestinal hypoperistalsis syndrome 1 2021-08-27 criteria provided, single submitter clinical testing

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