Submissions for variant NM_000432.4(MYL2):c.308T>G (p.Phe103Cys)

dbSNP: rs547860537

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000172054	SCV000054782	uncertain significance	not provided	2013-06-24	criteria provided, single submitter	research
GeneDx	RCV000172054	SCV000208862	uncertain significance	not provided	2020-11-04	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar (ClinVar Variant ID# 181433; Landrum et al., 2016)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001086360	SCV000549159	likely benign	Hypertrophic cardiomyopathy 10	2024-11-04	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001184261	SCV001350208	uncertain significance	Cardiomyopathy	2023-09-27	criteria provided, single submitter	clinical testing	This missense variant replaces phenylalanine with cysteine at codon 103 of the MYL2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in one individual affected with hypertrophic cardiomyopathy (PMID: 33029862). This variant occurs at an elevated allele frequency in the general population and has been identified in 30/251494 chromosomes (30/30616 South Asian chromosomes) 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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001184261	SCV002042753	likely benign	Cardiomyopathy	2019-11-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002321668	SCV002608908	uncertain significance	Cardiovascular phenotype	2018-12-14	criteria provided, single submitter	clinical testing	The p.F103C variant (also known as c.308T>G), located in coding exon 5 of the MYL2 gene, results from a T to G substitution at nucleotide position 308. The phenylalanine at codon 103 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been reported as a secondary cardiac variant in an exome cohort (Ng D et al. Circ Cardiovasc Genet, 2013 Aug;6:337-46). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health	RCV003998375	SCV004845840	uncertain significance	Hypertrophic cardiomyopathy	2023-12-13	criteria provided, single submitter	clinical testing	This missense variant replaces phenylalanine with cysteine at codon 103 of the MYL2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in one individual affected with hypertrophic cardiomyopathy (PMID: 33029862). This variant occurs at an elevated allele frequency in the general population and has been identified in 30/251494 chromosomes (30/30616 South Asian chromosomes) 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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV004017443	SCV004848315	likely benign	not specified	2019-10-14	criteria provided, single submitter	clinical testing	The p.Phe86Ser variant in MYL2 is classified as likely benign because it has been identified in 0.098% (30/30616) of South Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BS1.