Submissions for variant NM_053025.4(MYLK):c.601C>T (p.Leu201=)

gnomAD frequency: 0.00007  dbSNP: rs773082759

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000526771	SCV000440340	uncertain significance	Aortic aneurysm, familial thoracic 7	2018-01-12	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000526771	SCV000650567	benign	Aortic aneurysm, familial thoracic 7	2024-01-11	criteria provided, single submitter	clinical testing
GeneDx	RCV001576377	SCV001803548	uncertain significance	not provided	2022-11-04	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003485578	SCV004239518	benign	Familial thoracic aortic aneurysm and aortic dissection	2023-06-20	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003950202	SCV004765324	likely benign	MYLK-related disorder	2019-10-28	no assertion criteria provided	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).