Submissions for variant NM_000432.4(MYL2):c.359G>A (p.Arg120Gln)

gnomAD frequency: 0.00009  dbSNP: rs192057022

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000228967	SCV000284830	uncertain significance	Hypertrophic cardiomyopathy 10	2025-01-22	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 120 of the MYL2 protein (p.Arg120Gln). This variant is present in population databases (rs192057022, gnomAD 0.02%). This missense change has been observed in individual(s) with restrictive cardiomyopathy, hypertrophic cardiomyopathy or dilated cardiomyopathy (PMID: 22260945, 36264615, 38540378). ClinVar contains an entry for this variant (Variation ID: 36645). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Ambry Genetics	RCV000618181	SCV000740184	likely benign	Cardiovascular phenotype	2022-03-24	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.
CeGaT Center for Human Genetics Tuebingen	RCV000994981	SCV001148829	uncertain significance	not provided	2019-04-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001185060	SCV001351199	uncertain significance	Cardiomyopathy	2024-01-16	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with glutamine at codon 120 of the MYL2 protein. Computational prediction tools indicate that this variant has a neutral impact on protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in two individuals affected with restrictive cardiomyopathy (PMID: 22260945). This variant has been identified in 16/282870 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.
Fulgent Genetics, Fulgent Genetics	RCV002482922	SCV002796993	uncertain significance	Hypertrophic cardiomyopathy 10; Myopathy, myofibrillar, 12, infantile-onset, with cardiomyopathy	2021-08-06	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001185060	SCV003837854	uncertain significance	Cardiomyopathy	2021-12-29	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003996131	SCV004845834	uncertain significance	Hypertrophic cardiomyopathy	2024-09-17	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with glutamine at codon 120 of the MYL2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in two individuals affected with restrictive cardiomyopathy (PMID: 22260945). This variant has been identified in 16/282870 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	RCV000030324	SCV000052991	uncertain significance	Primary familial hypertrophic cardiomyopathy	2015-10-02	no assertion criteria provided	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036398	SCV000060053	uncertain significance	not specified	2008-07-14	no assertion criteria provided	clinical testing