Submissions for variant NM_000256.3(MYBPC3):c.238G>A (p.Ala80Thr)

dbSNP: rs730880700

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000158454	SCV000208389	uncertain significance	not provided	2024-08-19	criteria provided, single submitter	clinical testing	Identified in patients with HCM in published literature (PMID: 37652022, 35626289); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 37652022, 35626289)
Color Diagnostics, LLC DBA Color Health	RCV001181610	SCV001346791	uncertain significance	Cardiomyopathy	2019-11-05	criteria provided, single submitter	clinical testing	This missense variant replaces alanine with threonine at codon 80 of the MYBPC3 protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold ≤0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed 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.
Ambry Genetics	RCV002426776	SCV002731937	uncertain significance	Cardiovascular phenotype	2019-10-31	criteria provided, single submitter	clinical testing	The p.A80T variant (also known as c.238G>A), located in coding exon 2 of the MYBPC3 gene, results from a G to A substitution at nucleotide position 238. The alanine at codon 80 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV002484972	SCV002776621	uncertain significance	Hypertrophic cardiomyopathy 4; Left ventricular noncompaction 10	2021-08-12	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002515069	SCV003030149	uncertain significance	Hypertrophic cardiomyopathy	2024-05-21	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 80 of the MYBPC3 protein (p.Ala80Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 35626289). ClinVar contains an entry for this variant (Variation ID: 181134). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
All of Us Research Program, National Institutes of Health	RCV002515069	SCV004844965	uncertain significance	Hypertrophic cardiomyopathy	2023-09-05	criteria provided, single submitter	clinical testing	This missense variant replaces alanine with threonine at codon 80 of the MYBPC3 protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <=0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed 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.