ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.5422G>A (p.Asp1808Asn)

gnomAD frequency: 0.00002  dbSNP: rs571739078
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001944962 SCV002135621 benign Adams-Oliver syndrome 5 2024-10-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV002343923 SCV002649364 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2019-06-27 criteria provided, single submitter clinical testing The p.D1808N variant (also known as c.5422G>A), located in coding exon 29 of the NOTCH1 gene, results from a G to A substitution at nucleotide position 5422. The aspartic acid at codon 1808 is replaced by asparagine, an amino acid with highly similar properties. 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 RCV002478160 SCV002786877 uncertain significance Aortic valve disease 1; Adams-Oliver syndrome 5 2021-10-11 criteria provided, single submitter clinical testing
GeneDx RCV005225534 SCV005870413 uncertain significance not provided 2024-08-22 criteria provided, single submitter clinical testing Has been reported in association with TAAD and PAH, although some of these individuals had several variants in other genes (PMID: 34498425, 35811711, 34668355); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 34498425, 35811711, 34668355, 30111351)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV005225534 SCV005876468 uncertain significance not provided 2024-02-16 criteria provided, single submitter clinical testing The NOTCH1 c.5422G>A; p.Asp1808Asn variant (rs571739078) is reported in the literature in individuals affected with thoracic aortic aneurysm and dissection, pulmonary arterial hypertension, and intracranial aneurysm (Li 2021, Liang 2022, Song 2022). This variant is reported in ClinVar (Variation ID: 1367026). This variant is found in the general population with an overall allele frequency of 0.004% (12/280,046 alleles) in the Genome Aggregation Database (v2.1.1), but is considered a low confidence variant in the database. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.381). Due to limited information, the clinical significance of this variant is uncertain at this time. References: Li J et al. Genetic testing and clinical relevance of patients with thoracic aortic aneurysm and dissection in northwestern China. Mol Genet Genomic Med. 2021 Oct;9(10):e1800. PMID: 34498425. Liang KW et al. Whole Exome Sequencing of Patients With Heritable and Idiopathic Pulmonary Arterial Hypertension in Central Taiwan. Front Cardiovasc Med. 2022 Jun 22;9:911649. PMID: 35811711. Song Y et al. Whole Exome Sequencing in Patients with Phenotypically Associated Familial Intracranial Aneurysm. Korean J Radiol. 2022 Jan;23(1):101-111. PMID: 34668355.
Department of Pathology and Laboratory Medicine, Sinai Health System RCV002478160 SCV006053386 uncertain significance Aortic valve disease 1; Adams-Oliver syndrome 5 2022-05-06 criteria provided, single submitter research

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