Submissions for variant NM_053025.4(MYLK):c.4194C>T (p.His1398=)

gnomAD frequency: 0.02481  dbSNP: rs17298941

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000217763	SCV000269305	benign	not specified	2013-04-04	criteria provided, single submitter	clinical testing	His1398His in exon 24 of MYLK: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 3.9% (339/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs17298941).
PreventionGenetics, part of Exact Sciences	RCV000217763	SCV000315296	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000462804	SCV000440285	benign	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV000217763	SCV000525869	benign	not specified	2016-09-26	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000462804	SCV000560697	benign	Aortic aneurysm, familial thoracic 7	2025-02-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002315648	SCV000738321	benign	Familial thoracic aortic aneurysm and aortic dissection	2015-02-20	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001812228	SCV000884194	benign	not provided	2024-11-25	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000217763	SCV001361252	benign	not specified	2019-08-24	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001812228	SCV005303590	benign	not provided		criteria provided, single submitter	not provided
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000217763	SCV006066527	benign	not specified	2025-04-09	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000217763	SCV001808347	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000217763	SCV001930752	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000217763	SCV001952643	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000217763	SCV001972290	benign	not specified		no assertion criteria provided	clinical testing