ClinVar Miner

Submissions for variant NM_006180.6(NTRK2):c.746C>A (p.Ser249Tyr)

gnomAD frequency: 0.00006  dbSNP: rs772111782
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001767510 SCV001998366 uncertain significance not provided 2021-04-14 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Reported in individuals with obesity (Serra-Juhe et al., 2020); This variant is associated with the following publications: (PMID: 30926952)
Genetic Services Laboratory, University of Chicago RCV001821984 SCV002072064 uncertain significance not specified 2017-07-12 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001767510 SCV002486876 benign not provided 2024-01-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV002544081 SCV003719383 likely benign Inborn genetic diseases 2021-10-15 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences RCV004746443 SCV005363262 uncertain significance NTRK2-related disorder 2024-08-14 no assertion criteria provided clinical testing The NTRK2 c.746C>A variant is predicted to result in the amino acid substitution p.Ser249Tyr. This variant was reported in three individuals with early onset obesity; however, no additional information was provided to support the pathogenicity of this variant (Table S4, Serra-Juhé et al. 2019. PubMed ID: 30926952; Supplementary Table 1, Roberts KJ et al 2022. PubMed ID: 35562395). This variant is reported in 0.075% of alleles in individuals of Latino descent in gnomAD, which is more common than expected for a variant associated with autosomal dominant 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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