Submissions for variant NM_014391.3(ANKRD1):c.234A>T (p.Arg78Ser)

gnomAD frequency: 0.00017  dbSNP: rs141376679

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000150160	SCV000197050	uncertain significance	not specified	2014-04-04	criteria provided, single submitter	clinical testing	The Arg78Ser variant in ANKRD1 has not been reported in individuals with cardiom yopathy, but has been identified in 1/8598 of European American chromosomes by t he NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs14 1376679). Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive e nough to determine pathogenicity. Additional information is needed to fully asse ss the clinical significance of the Arg78Ser variant.
GeneDx	RCV000766414	SCV000512051	uncertain significance	not provided	2024-09-10	criteria provided, single submitter	clinical testing	Identified in a patient with DCM in the published literature (PMID: 32880476); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32880476)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000560866	SCV000658934	uncertain significance	ANKRD1-related dilated cardiomyopathy	2024-12-04	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 78 of the ANKRD1 protein (p.Arg78Ser). This variant is present in population databases (rs141376679, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 32880476). ClinVar contains an entry for this variant (Variation ID: 162750). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt ANKRD1 protein function with a negative predictive value of 80%. 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	RCV000766414	SCV002541091	uncertain significance	not provided	2021-10-27	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002426710	SCV002731902	uncertain significance	Cardiovascular phenotype	2023-01-08	criteria provided, single submitter	clinical testing	The p.R78S variant (also known as c.234A>T), located in coding exon 3 of the ANKRD1 gene, results from an A to T substitution at nucleotide position 234. The arginine at codon 78 is replaced by serine, an amino acid with dissimilar properties. 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 alteration remains unclear.