Submissions for variant NM_053025.4(MYLK):c.3898G>A (p.Ala1300Thr) (rs149530842)

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Clinical Services Laboratory,Illumina	RCV000528252	SCV000440290	uncertain significance	Aortic aneurysm, familial thoracic 7	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae	RCV000528252	SCV000650547	likely benign	Aortic aneurysm, familial thoracic 7	2019-12-31	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000528252	SCV000678226	uncertain significance	Aortic aneurysm, familial thoracic 7	2017-08-01	criteria provided, single submitter	clinical testing	MYLK NM_053026 exon22 p.Ala1231Thr (c.3691G>A): This variant has not been reported in the literature but is present in 0.1% (58/34412) of Latino chromosomes in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs149530842). This variant is present in ClinVar (Variation ID:342880). This variant threonine (Thr) 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	RCV000615774	SCV000717505	likely benign	not specified	2017-09-27	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics	RCV000620056	SCV000739289	uncertain significance	Cardiovascular phenotype	2017-09-06	criteria provided, single submitter	clinical testing	Insufficient evidence
Center for Human Genetics, Inc,Center for Human Genetics, Inc	RCV000659949	SCV000781853	likely benign	Connective tissue disease	2016-11-01	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario	RCV001170118	SCV001332657	benign	Familial thoracic aortic aneurysm and aortic dissection	2019-04-11	criteria provided, single submitter	clinical testing