Submissions for variant NM_002474.3(MYH11):c.3928G>A (p.Val1310Met)

gnomAD frequency: 0.00216  dbSNP: rs7196804

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000417389	SCV000234858	likely benign	not specified	2017-09-27	criteria provided, single submitter	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.
Ambry Genetics	RCV000182512	SCV000319366	benign	Cardiovascular phenotype	2016-03-03	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;Insufficient or conflicting evidence
Illumina Laboratory Services, Illumina	RCV000398079	SCV000395294	uncertain significance	Lissencephaly, Recessive	2016-06-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000459113	SCV000556093	likely benign	Aortic aneurysm, familial thoracic 4	2024-01-27	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000417389	SCV000702026	likely benign	not specified	2016-10-26	criteria provided, single submitter	clinical testing
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000680555	SCV000807967	likely benign	Connective tissue disorder	2018-06-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000757516	SCV000885770	likely benign	not provided	2018-06-29	criteria provided, single submitter	clinical testing	The MYH11 c.3928G>A p.Val1310Met variant (rs7196804), is reported in the literature in patients with aortopathies and classified as likely benign. This variant is found in the African population with an overall allele frequency of 0.52% (125/24024 alleles, but 0 homozygotes) in the Genome Aggregation Database, and is found in ClinVar (Variation ID: 201068). The valine at codon 1310 is highly conserved, but computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Based on available information, this variant is considered to be likely benign.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000459113	SCV000898837	uncertain significance	Aortic aneurysm, familial thoracic 4	2018-02-08	criteria provided, single submitter	clinical testing	MYH11 NM_002474.2 exon 29 p.Val1310Met (c.3928G>A): This variant has not been reported in the literature but is present in 0.5% (125/24024) of African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs7196804). This variant is present in ClinVar, with several labs classifying this variant as likely benign or benign(Variation ID:201068). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769666	SCV000901076	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2017-05-12	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000769666	SCV000904522	benign	Familial thoracic aortic aneurysm and aortic dissection	2018-10-15	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001116425	SCV001274498	likely benign	Lissencephaly 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 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.
Illumina Laboratory Services, Illumina	RCV000459113	SCV001279944	benign	Aortic aneurysm, familial thoracic 4	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224200	SCV003920232	uncertain significance	Aortic aneurysm, familial thoracic 4; Visceral myopathy 2; Megacystis-microcolon-intestinal hypoperistalsis syndrome 2	2021-03-30	criteria provided, single submitter	clinical testing	MYH11 NM_002474.2 exon 29 p.Val1310Met (c.3928G>A): This variant has not been reported in the literature but is present in 0.5% (125/24024) of African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs7196804). This variant is present in ClinVar, with several labs classifying this variant as likely benign or benign(Variation ID:201068). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
CeGaT Center for Human Genetics Tuebingen	RCV000757516	SCV004184539	likely benign	not provided	2024-03-01	criteria provided, single submitter	clinical testing	MYH11: BS1
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000757516	SCV001800124	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000417389	SCV001808042	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000757516	SCV001974446	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000757516	SCV002033861	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003927709	SCV004739540	likely benign	MYH11-related disorder	2019-04-15	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).