Submissions for variant NM_053025.4(MYLK):c.1048G>A (p.Ala350Thr)

dbSNP: rs532659627

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001052945	SCV001217181	uncertain significance	Aortic aneurysm, familial thoracic 7	2023-06-03	criteria provided, single submitter	clinical testing	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. 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. ClinVar contains an entry for this variant (Variation ID: 849061). This variant has not been reported in the literature in individuals affected with MYLK-related conditions. This variant is present in population databases (rs532659627, gnomAD 0.007%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 350 of the MYLK protein (p.Ala350Thr).
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001170672	SCV001333266	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2018-09-12	criteria provided, single submitter	clinical testing
GeneDx	RCV001772264	SCV002004674	uncertain significance	not provided	2021-08-19	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 does not alter protein structure/function; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 849061; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 26582918)
Ambry Genetics	RCV001170672	SCV002707868	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2022-04-03	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.