ClinVar Miner

Submissions for variant NM_002880.4(RAF1):c.785A>T (p.Asn262Ile)

dbSNP: rs730881010
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159095 SCV000209038 likely pathogenic not provided 2023-04-17 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are often considered pathogenic (HGMD); This variant is associated with the following publications: (PMID: 24451042, 24957944, 9689060, 15520807, 17603483, 17603482, 29493581, 19020799)
Blueprint Genetics RCV000159095 SCV000927370 likely pathogenic not provided 2017-08-09 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001232030 SCV001404573 likely pathogenic RASopathy 2020-12-04 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Asn262 amino acid residue in RAF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20052757, 30732632). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. This variant has been observed in an individual with clinical features of RAF1-related condition (PMID: 24451042). ClinVar contains an entry for this variant (Variation ID: 181517). This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with isoleucine at codon 262 of the RAF1 protein (p.Asn262Ile). The asparagine residue is highly conserved and there is a large physicochemical difference between asparagine and isoleucine.

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