Submissions for variant NM_032578.4(MYPN):c.1103G>A (p.Gly368Asp)

gnomAD frequency: 0.00006  dbSNP: rs555527385

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV001256882	SCV001433378	uncertain significance	Dilated cardiomyopathy 1A	2020-02-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002430060	SCV002743061	uncertain significance	Cardiovascular phenotype	2022-05-24	criteria provided, single submitter	clinical testing	The p.G368D variant (also known as c.1103G>A), located in coding exon 3 of the MYPN gene, results from a G to A substitution at nucleotide position 1103. The glycine at codon 368 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is conserved. 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.
Invitae	RCV002570612	SCV003269687	uncertain significance	Dilated cardiomyopathy 1KK	2022-06-15	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 368 of the MYPN protein (p.Gly368Asp). This variant is present in population databases (rs555527385, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with MYPN-related conditions. ClinVar contains an entry for this variant (Variation ID: 978346). 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: "Possibly Damaging"; 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.
GeneDx	RCV003227019	SCV003923835	uncertain significance	not provided	2022-11-08	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
CeGaT Center for Human Genetics Tuebingen	RCV003227019	SCV004126618	uncertain significance	not provided	2022-12-01	criteria provided, single submitter	clinical testing