ClinVar Miner

Submissions for variant NM_002474.3(MYH11):c.5628T>A (p.Asn1876Lys)

gnomAD frequency: 0.00001  dbSNP: rs769802444
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001314929 SCV001505481 uncertain significance Aortic aneurysm, familial thoracic 4 2024-03-06 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 1883 of the MYH11 protein (p.Asn1883Lys). This variant is present in population databases (rs769802444, gnomAD 0.006%). 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: 1015991). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MYH11 protein function with a negative predictive value of 95%. 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.
Fulgent Genetics, Fulgent Genetics RCV002504482 SCV002816372 uncertain significance Aortic aneurysm, familial thoracic 4; Visceral myopathy 2; Megacystis-microcolon-intestinal hypoperistalsis syndrome 2 2021-10-08 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004005076 SCV004826024 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-05-15 criteria provided, single submitter clinical testing This missense variant replaces asparagine with lysine at codon 1883 of the MYH11 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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 2/250858 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.

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