Submissions for variant NM_002474.3(MYH11):c.4579-5G>A

dbSNP: rs759760029

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000367942	SCV000395253	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000396166	SCV000395254	uncertain significance	Lissencephaly, Recessive	2016-06-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000641587	SCV000763229	uncertain significance	Aortic aneurysm, familial thoracic 4	2024-05-25	criteria provided, single submitter	clinical testing	This sequence change falls in intron 33 of the MYH11 gene. It does not directly change the encoded amino acid sequence of the MYH11 protein. This variant is not present in population databases (gnomAD no frequency). 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: 318111). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Illumina Laboratory Services, Illumina	RCV000641587	SCV001279808	uncertain significance	Aortic aneurysm, familial thoracic 4	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	RCV001548504	SCV001768426	likely benign	not provided	2021-02-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000367942	SCV002052856	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2023-02-21	criteria provided, single submitter	clinical testing	This variant causes a G to A nucleotide substitution at the -5 position of intron 33 of the MYH11 gene. 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 not been identified 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.
Ambry Genetics	RCV000367942	SCV002638555	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2021-10-15	criteria provided, single submitter	clinical testing	The c.4579-5G>A intronic variant results from a G to A substitution 5 nucleotides upstream from coding exon 32 in the MYH11 gene. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will result in the creation or strengthening of a novel splice acceptor site. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.