ClinVar Miner

Submissions for variant NM_006180.6(NTRK2):c.1456G>A (p.Val486Ile)

gnomAD frequency: 0.00004  dbSNP: rs201028496
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002009019 SCV002268253 uncertain significance not provided 2024-10-13 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 486 of the NTRK2 protein (p.Val486Ile). This variant is present in population databases (rs201028496, gnomAD 0.02%). This missense change has been observed in individual(s) with severe obesity (PMID: 35061034). ClinVar contains an entry for this variant (Variation ID: 1488029). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt NTRK2 protein function with a negative predictive value of 80%. 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.
PreventionGenetics, part of Exact Sciences RCV004746566 SCV005354636 uncertain significance NTRK2-related disorder 2024-05-28 no assertion criteria provided clinical testing The NTRK2 c.1456G>A variant is predicted to result in the amino acid substitution p.Val486Ile. This variant was reported in an individual with severe obesity, but was classified as a variant of uncertain significance (Saeed et al. 2022. PubMed ID: 35061034). This variant is reported in 0.016% of alleles in individuals of South Asian descent in gnomAD, which may be too common to be a primary cause of disease. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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