ClinVar Miner

Submissions for variant NM_002470.4(MYH3):c.700G>A (p.Ala234Thr)

gnomAD frequency: 0.00001  dbSNP: rs121913623
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000486376 SCV000567161 likely pathogenic not provided 2017-05-10 criteria provided, single submitter clinical testing The A234T variant in the MYH3 gene has been reported previously in the heterozygous state in individuals with distal arthrogryposis type 1 (DA1) and distal arthrogryposis type 2B (DA2B) (Tajsharghi et al., 2008; Kimber et al., 2012; Beck et al., 2013). Intrafamilial variable expression of DA1 and DA2B in related individuals harboring A234T has been reported (Kimber et al., 2012). The A234T variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A234T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret A234T as a likely pathogenic variant.
Fulgent Genetics, Fulgent Genetics RCV000762979 SCV000893424 likely pathogenic Freeman-Sheldon syndrome; Distal arthrogryposis type 2B1; Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A 2018-10-31 criteria provided, single submitter clinical testing
OMIM RCV000015208 SCV000035465 pathogenic Arthrogryposis, distal, type 2B3 2008-08-01 no assertion criteria provided literature only

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