ClinVar Miner

Submissions for variant NM_005188.4(CBL):c.2708A>G (p.His903Arg)

dbSNP: rs1950088762
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001813654 SCV002060764 uncertain significance Noonan syndrome and Noonan-related syndrome 2019-06-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001869615 SCV002203668 uncertain significance RASopathy 2021-08-31 criteria provided, single submitter clinical testing 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. 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 CBL protein function. This variant has not been reported in the literature in individuals affected with CBL-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with arginine at codon 903 of the CBL protein (p.His903Arg). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and arginine.
GeneDx RCV004762188 SCV005371157 uncertain significance not provided 2023-06-09 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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