ClinVar Miner

Submissions for variant NM_002474.3(MYH11):c.4372G>A (p.Ala1458Thr)

gnomAD frequency: 0.00003  dbSNP: rs775154820
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV003528163 SCV000319350 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2024-10-28 criteria provided, single submitter clinical testing The c.4372G>A (p.A1458T) alteration is located in exon 32 (coding exon 31) of the MYH11 gene. This alteration results from a G to A substitution at nucleotide position 4372, causing the alanine (A) at amino acid position 1458 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001220318 SCV001392298 uncertain significance Aortic aneurysm, familial thoracic 4 2022-02-18 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1465 of the MYH11 protein (p.Ala1465Thr). This variant is present in population databases (rs775154820, gnomAD 0.002%). 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: 263876). 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.
Color Diagnostics, LLC DBA Color Health RCV003528163 SCV004359357 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-09-28 criteria provided, single submitter clinical testing This missense variant replaces alanine with threonine at codon 1465 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 2/251420 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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