Submissions for variant NM_000432.4(MYL2):c.483C>A (p.His161Gln)

dbSNP: rs886039108

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000247783	SCV000320072	uncertain significance	Cardiovascular phenotype	2015-08-13	criteria provided, single submitter	clinical testing	The p.H161Q variant (also known as c.483C>A), located in coding exon 7 of the MYL2 gene, results from a C to A substitution at nucleotide position 483. The histidine at codon 161 is replaced by glutamine, an amino acid with highly similar properties. This variant has not been previously reported in association with hypertrophic cardiomyopathy (HCM). Another alteration in the same codon, p.H161R (c.482A>G), has been reported in association with HCM (Helms AS et al. Circ Cardiovasc Genet. 2014; 7(4):434-43). The p.H161Q variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001209885	SCV001381341	uncertain significance	Hypertrophic cardiomyopathy 10	2022-06-13	criteria provided, single submitter	clinical testing	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. 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: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 264266). This variant has not been reported in the literature in individuals affected with MYL2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 161 of the MYL2 protein (p.His161Gln).
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001726080	SCV001963438	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001726080	SCV001972852	pathogenic	not provided		no assertion criteria provided	clinical testing