Submissions for variant NM_002474.3(MYH11):c.4855AAG[2] (p.Lys1621del)

dbSNP: rs755547393

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000704502	SCV000833453	uncertain significance	Aortic aneurysm, familial thoracic 4	2024-09-14	criteria provided, single submitter	clinical testing	This variant, c.4882_4884del, results in the deletion of 1 amino acid(s) of the MYH11 protein (p.Lys1628del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs755547393, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with MYH11-related conditions. ClinVar contains an entry for this variant (Variation ID: 580843). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color Diagnostics, LLC DBA Color Health	RCV001176310	SCV001340229	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2023-01-26	criteria provided, single submitter	clinical testing	This variant causes a deletion of a single amino acid in the MYH11 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 17/282850 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001193454	SCV001362293	likely benign	not specified	2019-06-17	criteria provided, single submitter	clinical testing	Variant summary: MYH11 c.4882_4884delAAG (p.Lys1628del) results in an in-frame deletion that is predicted to remove 1 amino acid from the encoded protein. The variant allele was found at a frequency of 5.2e-05 in 251476 control chromosomes (gnomAD). The observed variant frequency is approximately 41 fold of the estimated maximal expected allele frequency for a pathogenic variant in MYH11 causing Aortopathy phenotype (1.3e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.4882_4884delAAG in individuals affected with Aortopathy and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submitter (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV003392541	SCV004120365	uncertain significance	MYH11-related disorder	2023-07-21	criteria provided, single submitter	clinical testing	The MYH11 c.4882_4884delAAG variant is predicted to result in an in-frame deletion (p.Lys1628del). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% of alleles in individuals of European (Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-15814097-GCTT-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Ambry Genetics	RCV001176310	SCV005139086	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2024-03-27	criteria provided, single submitter	clinical testing	The c.4861_4863delAAG variant (also known as p.K1621del) is located in coding exon 33 of the MYH11 gene. This variant results from an in-frame AAG deletion at nucleotide positions 4861 to 4863. This results in the in-frame deletion of a lysine at codon 1621. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Based on the available evidence, the clinical significance of this alteration remains unclear.
Mayo Clinic Laboratories, Mayo Clinic	RCV004792413	SCV005411254	uncertain significance	not provided	2023-11-16	criteria provided, single submitter	clinical testing	BP3