ClinVar Miner

Submissions for variant NM_053025.4(MYLK):c.399G>T (p.Gln133His)

gnomAD frequency: 0.00167  dbSNP: rs140148380
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Total submissions: 16
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001170677 SCV000319429 likely benign Familial thoracic aortic aneurysm and aortic dissection 2019-02-16 criteria provided, single submitter clinical testing This alteration is classified as likely 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.
Illumina Laboratory Services, Illumina RCV001000031 SCV000440346 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.
GeneDx RCV001579449 SCV000536063 likely benign not provided 2021-05-07 criteria provided, single submitter clinical testing
Invitae RCV001000031 SCV000560694 benign Aortic aneurysm, familial thoracic 7 2024-02-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001579449 SCV000604385 benign not provided 2021-09-01 criteria provided, single submitter clinical testing
CSER _CC_NCGL, University of Washington RCV001795472 SCV000700124 likely benign Congenital aneurysm of ascending aorta 2016-10-01 criteria provided, single submitter research Found in patient having exome sequencing for an unrelated indication. No known history of familial thoracic aortic aneurysm. This interpretation considers GERP score and allele frequency data, in addition to published reports of the variant in the literature, available at the time of review.
Eurofins Ntd Llc (ga) RCV000427577 SCV000701929 likely benign not specified 2016-11-03 criteria provided, single submitter clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV000427577 SCV000740627 likely benign not specified 2017-06-13 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001170677 SCV001333271 benign Familial thoracic aortic aneurysm and aortic dissection 2017-12-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000427577 SCV001338667 likely benign not specified 2020-04-27 criteria provided, single submitter clinical testing Variant summary: MYLK c.399G>T (p.Gln133His) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0018 in 251440 control chromosomes in the gnomAD database, including 3 homozygotes. The observed variant frequency is approximately 725 fold of the estimated maximal expected allele frequency for a pathogenic variant in MYLK causing Aortopathy phenotype (2.5e-06), strongly suggesting that the variant is benign. c.399G>T has been reported in the literature (Milewicz_2017). This report however, does not provide unequivocal conclusions about association of the variant with Aortopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Eight ClinVar submitters (evaluation after 2014) cite the variant as likely benign/benign (n=7) or uncertain significance (n=1). Based on the evidence outlined above, the variant was classified as likely benign.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV001579449 SCV002011111 benign not provided 2021-11-03 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001579449 SCV004011483 likely benign not provided 2024-01-01 criteria provided, single submitter clinical testing MYLK: BP4, BS2
PreventionGenetics, part of Exact Sciences RCV003909883 SCV004720666 likely benign MYLK-related disorder 2019-05-29 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV001579449 SCV001807279 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV001579449 SCV001929757 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001579449 SCV001965879 likely benign not provided no assertion criteria provided clinical testing

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