ClinVar Miner

Submissions for variant NM_002474.3(MYH11):c.2924C>T (p.Thr975Met)

gnomAD frequency: 0.00003  dbSNP: rs763795192
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000659908 SCV000781812 uncertain significance Connective tissue disorder 2016-11-01 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002477473 SCV000896508 uncertain significance Aortic aneurysm, familial thoracic 4; Visceral myopathy 2; Megacystis-microcolon-intestinal hypoperistalsis syndrome 2 2021-08-27 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000765255 SCV002166881 uncertain significance Aortic aneurysm, familial thoracic 4 2022-10-20 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 982 of the MYH11 protein (p.Thr982Met). This variant is present in population databases (rs763795192, 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: 547541). 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. 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.
PreventionGenetics, part of Exact Sciences RCV003424265 SCV004107458 uncertain significance MYH11-related disorder 2023-02-02 criteria provided, single submitter clinical testing The MYH11 c.2945C>T variant is predicted to result in the amino acid substitution p.Thr982Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.016% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-15833981-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
All of Us Research Program, National Institutes of Health RCV004004200 SCV004817410 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2024-07-20 criteria provided, single submitter clinical testing This missense variant replaces threonine with methionine at codon 982 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 6/282892 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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