Description
Variant summary: MYH9 c.3340T>C (p.Ser1114Pro) results in a non-conservative amino acid change located in the Myosin tail domain (IPR002928) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00035 in 1613794 control chromosomes in the gnomAD v3 database, including 1 homozygote. c.3340T>C has been reported in the literature in individuals affected with Alport syndrome with macrothrombocytopenia, Hereditary chronic kidney disease or Hearing loss (Heath_2001, Sheppard_2018, Popp_2022). These reports do not provide unequivocal conclusions about association of the variant with Macrothrombocytopenia And Granulocyte Inclusions With Or Without Nephritis Or Sensorineural Hearing Loss. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 30245029, 11590545, 36100708, 29907799). Six submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified this variant as uncertain significance (n=2) and likely benign (n=4). Based on the evidence outlined above, the variant was classified as likely benign.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
