ClinVar Miner

Submissions for variant NM_004333.6(BRAF):c.1027C>T (p.Pro343Ser)

gnomAD frequency: 0.00001  dbSNP: rs758935249
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000589715 SCV000577247 likely benign not provided 2020-11-20 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 30050098, 29907801)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589715 SCV000698330 uncertain significance not provided 2016-03-29 criteria provided, single submitter clinical testing Variant summary: The c.1027C>T is a missense variant involves a highly conserved nucleotide. 3/4 in silico tools predict a deleterious outcome (SNPs&GO not captured due to low reliability index). This variant has not been reported in association with NRSD in any publication or dbs. The observed allele frequency of this variant in general population is 3/121412 chr, 0.0025% (0.0045% in European non-Finnish), which is higher than calculated maximum disease allele frequency (0.00025%) for pathogenic BRAF variant, suggesting that this variant may be a rare functional polymorphism. In addition, the variant is located outside of any known functional domain. Taken together, variant shows some evidence of neutrality, but in the absence of clinical, functional data, the variant is classified as a possibly benign variant until more information becomes available.
Labcorp Genetics (formerly Invitae), Labcorp RCV003654409 SCV004551816 uncertain significance RASopathy 2023-05-19 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 BRAF protein function. ClinVar contains an entry for this variant (Variation ID: 426721). This missense change has been observed in individual(s) with cystic hygroma (PMID: 29907801). This variant is present in population databases (rs758935249, gnomAD 0.005%). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 343 of the BRAF protein (p.Pro343Ser).

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