ClinVar Miner

Submissions for variant NM_020297.4(ABCC9):c.1329G>A (p.Met443Ile)

gnomAD frequency: 0.00003  dbSNP: rs151197166
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001049699 SCV001213766 uncertain significance Dilated cardiomyopathy 1O 2022-09-05 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 443 of the ABCC9 protein (p.Met443Ile). This variant is present in population databases (rs151197166, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ABCC9-related conditions. ClinVar contains an entry for this variant (Variation ID: 846402). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 RCV001759978 SCV001989599 uncertain significance not provided 2019-08-01 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function
Ambry Genetics RCV002379540 SCV002693031 uncertain significance Cardiovascular phenotype 2023-02-03 criteria provided, single submitter clinical testing The p.M443I variant (also known as c.1329G>A), located in coding exon 9 of the ABCC9 gene, results from a G to A substitution at nucleotide position 1329. The methionine at codon 443 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is well 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.
Fulgent Genetics, Fulgent Genetics RCV002489611 SCV002781634 uncertain significance Hypertrichotic osteochondrodysplasia Cantu type; Dilated cardiomyopathy 1O; Atrial fibrillation, familial, 12; Intellectual disability and myopathy syndrome 2021-10-13 criteria provided, single submitter clinical testing

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