ClinVar Miner

Submissions for variant NM_005188.4(CBL):c.2120C>G (p.Pro707Arg)

dbSNP: rs576175174
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, University of Goettingen RCV002246192 SCV002515871 uncertain significance CBL-related disorder 2022-05-20 criteria provided, single submitter clinical testing For the following reasons, the CBL sequence variant found is assessed by us as a "variant of unclear significance" (VUS) with a possibly pathogenic character: the mutation has not yet been described in the specialist literature or listed in the HGMD and ClinVar databases; a comparison with the gnomAD browser did not provide any evidence that this sequence change is a norm variant that can also be detected in non-affected individuals; the mutation is independently classified as deleterious by four prediction programs; the following ACMG criteria were used for classification: PM1, PM2, PP2, PP3.
Labcorp Genetics (formerly Invitae), Labcorp RCV003655349 SCV004375097 uncertain significance RASopathy 2023-11-04 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 707 of the CBL protein (p.Pro707Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CBL-related conditions. ClinVar contains an entry for this variant (Variation ID: 1684572). 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 with a negative predictive value of 95%. 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.
Ambry Genetics RCV004990749 SCV005545867 uncertain significance Cardiovascular phenotype 2024-06-28 criteria provided, single submitter clinical testing The c.2120C>G (p.P707R) alteration is located in exon 13 (coding exon 13) of the CBL gene. This alteration results from a C to G substitution at nucleotide position 2120, causing the proline (P) at amino acid position 707 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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