ClinVar Miner

Submissions for variant NM_053025.4(MYLK):c.554C>G (p.Thr185Ser) (rs1057518439)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000414313 SCV000492063 uncertain significance not specified 2016-11-22 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the MYLK gene. The T185S variant has not been published as a pathogenic variant or been reported as a benign variant to our knowledge. This variant was not observed in the Exome Aggregation Consortium or in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Although the T185S variant occurs at a position that is conserved across species, it is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign. This result cannot be interpreted for diagnosis or used for family member screening at this time.
Invitae RCV000807946 SCV000948026 uncertain significance Aortic aneurysm, familial thoracic 7 2018-10-10 criteria provided, single submitter clinical testing This sequence change replaces threonine with serine at codon 185 of the MYLK protein (p.Thr185Ser). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MYLK-related disease. ClinVar contains an entry for this variant (Variation ID: 373471). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55"). 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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