ClinVar Miner

Submissions for variant NM_002474.3(MYH11):c.4123G>A (p.Asp1375Asn)

gnomAD frequency: 0.00002  dbSNP: rs143467011
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000773560 SCV000907254 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-05-08 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with asparagine at codon 1382 of the MYH11 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MYH11-related disorders in the literature. This variant has been identified in 5/281040 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Invitae RCV001245253 SCV001418527 uncertain significance Aortic aneurysm, familial thoracic 4 2022-05-28 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1382 of the MYH11 protein (p.Asp1382Asn). This variant is present in population databases (rs143467011, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with MYH11-related conditions. ClinVar contains an entry for this variant (Variation ID: 628895). 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: "Deleterious"; PolyPhen-2: "Probably 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.
MGZ Medical Genetics Center RCV001245253 SCV002579997 uncertain significance Aortic aneurysm, familial thoracic 4 2022-05-19 criteria provided, single submitter clinical testing
Ambry Genetics RCV000773560 SCV002627156 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2022-01-19 criteria provided, single submitter clinical testing The p.D1375N variant (also known as c.4123G>A), located in coding exon 30 of the MYH11 gene, results from a G to A substitution at nucleotide position 4123. The aspartic acid at codon 1375 is replaced by asparagine, an amino acid with highly 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.

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