Submissions for variant NM_000258.3(MYL3):c.26A>G (p.Lys9Arg)

gnomAD frequency: 0.00001  dbSNP: rs1025864971

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000414165	SCV000492323	uncertain significance	not specified	2016-12-07	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the MYL3 gene. The K9R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant was not observed in the Exome Aggregation Consortium data set. However, the K9R variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved across species and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Color Diagnostics, LLC DBA Color Health	RCV000771980	SCV000904935	uncertain significance	Cardiomyopathy	2024-03-06	criteria provided, single submitter	clinical testing	This missense variant replaces lysine with arginine at codon 9 of the MYL3 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 not been reported in individuals affected with MYL3-related 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000800832	SCV000940568	uncertain significance	Hypertrophic cardiomyopathy	2022-02-12	criteria provided, single submitter	clinical testing	This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 9 of the MYL3 protein (p.Lys9Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MYL3-related conditions. ClinVar contains an entry for this variant (Variation ID: 373705). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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.
Mayo Clinic Laboratories, Mayo Clinic	RCV001509218	SCV001715819	uncertain significance	not provided	2020-06-09	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004022177	SCV003970135	uncertain significance	Cardiovascular phenotype	2024-03-01	criteria provided, single submitter	clinical testing	The p.K9R variant (also known as c.26A>G), located in coding exon 1 of the MYL3 gene, results from an A to G substitution at nucleotide position 26. The lysine at codon 9 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health	RCV000800832	SCV004843388	uncertain significance	Hypertrophic cardiomyopathy	2024-07-29	criteria provided, single submitter	clinical testing	This missense variant replaces lysine with arginine at codon 9 of the MYL3 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 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.