ClinVar Miner

Submissions for variant NM_002880.4(RAF1):c.1867C>T (p.Pro623Ser)

dbSNP: rs373596121
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000424840 SCV000536501 uncertain significance not provided 2020-05-26 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed in large population cohorts (Lek et al., 2016); The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); Located in exon 17, which encodes part of the CR3 domain and is recognized as an important functional region by the ClinGen RASopathy Expert Panel (Gelb et al., 2018)
Fulgent Genetics, Fulgent Genetics RCV002480331 SCV002777533 uncertain significance LEOPARD syndrome 2; Noonan syndrome 5; Dilated cardiomyopathy 1NN 2021-09-20 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003654278 SCV004412521 uncertain significance RASopathy 2023-05-22 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 623 of the RAF1 protein (p.Pro623Ser). This variant is present in population databases (rs373596121, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with RAF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 393135). 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 expected to disrupt RAF1 protein function. 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.

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