ClinVar Miner

Submissions for variant NM_053025.4(MYLK):c.1327C>T (p.Pro443Ser) (rs35156360)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000217065 SCV000269288 benign not specified 2013-04-04 criteria provided, single submitter clinical testing Pro443Ser in exon 11 of MYLK: This variant is not expected to have clinical sign ificance because it has been identified in 2.0% (176/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //; dbSNP rs35156360).
Invitae RCV000232645 SCV000291188 benign Aortic aneurysm, familial thoracic 7 2019-12-31 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000217065 SCV000315269 benign not specified criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000217065 SCV000338967 benign not specified 2016-02-05 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000232645 SCV000440329 likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000232645 SCV000604383 benign Aortic aneurysm, familial thoracic 7 2018-07-09 criteria provided, single submitter clinical testing
Ambry Genetics RCV000621719 SCV000738292 benign Cardiovascular phenotype 2015-01-30 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Integrated Genetics/Laboratory Corporation of America RCV000217065 SCV001361516 benign not specified 2019-09-25 criteria provided, single submitter clinical testing Variant summary: MYLK c.1327C>T (p.Pro443Ser) results in a non-conservative amino acid change located in one of the immunoglobulin subtype 2 domains (IPR003598) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.014 in 280644 control chromosomes (predominantly reported within the Ashkenazi Jewish and Non-Finnish European subpopulations) in the gnomAD database, including 35 homozygotes. The observed variant frequency within the gnomAD database is approximately 500 fold of the estimated maximal expected allele frequency for a pathogenic variant in MYLK causing Aortopathy phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism. Though the variant, c.1327C>T, has been reported to be found in a cohort of patients with familial abdominal aortic aneurysm, however, the variant was noted to be a part of complex genotypes, and it did not segregate with the disease in at least one family (van de Luijtgaarden_2015). To our knowledge no experimental evidence demonstrating its impact on protein function has been reported. Six ClinVar submissions (evaluation after 2014) cites the variant five times as benign and once as likely benign. Based on the evidence outlined above, the variant was classified as benign.
GeneDx RCV000217065 SCV000525093 benign not specified 2016-10-10 no assertion criteria provided 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.

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