ClinVar Miner

Submissions for variant NM_024753.5(TTC21B):c.2549C>T (p.Ala850Val)

gnomAD frequency: 0.00017  dbSNP: rs199795649
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001773078 SCV002003794 uncertain significance not provided 2021-04-02 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001868634 SCV002171483 uncertain significance Jeune thoracic dystrophy; Nephronophthisis 2024-12-02 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 850 of the TTC21B protein (p.Ala850Val). This variant is present in population databases (rs199795649, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with TTC21B-related conditions. ClinVar contains an entry for this variant (Variation ID: 1314569). 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 TTC21B protein function with a negative predictive value of 95%. 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.
Fulgent Genetics, Fulgent Genetics RCV002489807 SCV002785571 uncertain significance Asphyxiating thoracic dystrophy 4; Nephronophthisis 12 2024-04-25 criteria provided, single submitter clinical testing
Ambry Genetics RCV004968272 SCV005523477 uncertain significance Inborn genetic diseases 2024-11-29 criteria provided, single submitter clinical testing The c.2549C>T (p.A850V) alteration is located in exon 19 (coding exon 19) of the TTC21B gene. This alteration results from a C to T substitution at nucleotide position 2549, causing the alanine (A) at amino acid position 850 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV004734264 SCV005363883 uncertain significance TTC21B-related disorder 2024-09-25 no assertion criteria provided clinical testing The TTC21B c.2549C>T variant is predicted to result in the amino acid substitution p.Ala850Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.020% of alleles in individuals of African descent in gnomAD. 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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