ClinVar Miner

Submissions for variant NM_014391.3(ANKRD1):c.417C>A (p.Phe139Leu) (rs201398260)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000038852 SCV000062530 uncertain significance not specified 2012-10-24 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Phe139Leu varia nt in ANKRD1 has been identified by our laboratory in one individual with DCM, b ut did not segregate with disease in 1 affected relative. In addition, this vari ant has been identified in 1/186 Finnish chromosomes by the 1000 Genomes Sequenc ing Project (http://1000genomes.org; dbSNP rs201398260), though this could repre sent a presymptomatic individual. Phenylalanine (Phe) at this position is not co nserved in mammals or evolutionarily distant species, suggesting that a change a t this position may be tolerated. Additional computational analyses (biochemical amino acid properties, AlignGVGD, PolyPhen2, and SIFT) do not provide strong su pport for or against an impact to the protein. Although this data supports that the Phe139Leu variant may be benign, additional studies are needed to fully asse ss its clinical significance.
GeneDx RCV000767133 SCV000535718 uncertain significance not provided 2017-01-06 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ANKRD1 gene. The F139L variant has been reported in one patient with arrhythmogenic right ventricular cardiomyopathy (ARVC) diagnosed during an autopsy after sudden cardiac death who also harbored a missense variant in the CRYAB gene (Hertz et al., 2015). The F139L variant was observed in approximately 0.5% of alleles from individuals of European (Finnish) ancestry in the Exome Aggregation Consortium (ExAC) data set. The F139L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is only conserved in mammals. Nevertheless, in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. This result cannot be interpreted for diagnosis or used for family member screening at this time.
Invitae RCV000767133 SCV000658938 benign not provided 2018-07-02 criteria provided, single submitter clinical testing
Invitae RCV001514558 SCV001722430 benign ANKRD1-related dilated cardiomyopathy 2020-09-24 criteria provided, single submitter clinical testing

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