ClinVar Miner

Submissions for variant NM_024753.5(TTC21B):c.569T>A (p.Met190Lys)

gnomAD frequency: 0.00004  dbSNP: rs200374808
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002018472 SCV002303152 uncertain significance Jeune thoracic dystrophy; Nephronophthisis 2022-07-19 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 190 of the TTC21B protein (p.Met190Lys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 1513727). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
Ambry Genetics RCV004970792 SCV005523475 uncertain significance Inborn genetic diseases 2024-07-02 criteria provided, single submitter clinical testing The c.569T>A (p.M190K) alteration is located in exon 6 (coding exon 6) of the TTC21B gene. This alteration results from a T to A substitution at nucleotide position 569, causing the methionine (M) at amino acid position 190 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV004734399 SCV005344806 uncertain significance TTC21B-related disorder 2024-08-16 no assertion criteria provided clinical testing The TTC21B c.569T>A variant is predicted to result in the amino acid substitution p.Met190Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0018% of alleles in individuals of European (Non-Finnish) 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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