ClinVar Miner

Submissions for variant NM_003036.4(SKI):c.2183C>T (p.Pro728Leu) (rs372950890)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000196525 SCV000250687 uncertain significance not provided 2016-03-08 criteria provided, single submitter clinical testing The P728L variant has been previously reported in 4 probands of Filipino ancestry with cleft lip and/or palate (CL/P), and the variant was absent from 186 matched controls (Vieira A et al., 2005). In addition, P728L was not observed in approximately 3,300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Vieira et al. (2005) reported P728L occurred de novo in one family with a history of clefts. Nevertheless, the P728L variant did not segregate in another family with CL/P history; therefore, it was concluded P728L was a benign variant for this phenotype (Vieira et al., 2005). The P728L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved when present across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Finally, no missense mutations in nearby residues have been reported in association with SGS, suggesting this region of the protein may be tolerant of change.Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.
Invitae RCV000196525 SCV000760442 likely benign not provided 2018-12-07 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000638888 SCV000894752 uncertain significance Shprintzen-Goldberg syndrome 2018-10-31 criteria provided, single submitter clinical testing

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