Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001998611 | SCV002265807 | uncertain significance | not provided | 2023-12-11 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 257 of the TPRN protein (p.Pro257Leu). 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 TPRN-related conditions. ClinVar contains an entry for this variant (Variation ID: 1478433). 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 TPRN 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. |
| Fulgent Genetics, |
RCV002484905 | SCV002790680 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 79 | 2022-01-03 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002579513 | SCV003725318 | uncertain significance | Inborn genetic diseases | 2022-07-26 | criteria provided, single submitter | clinical testing | The c.770C>T (p.P257L) alteration is located in exon 1 (coding exon 1) of the TPRN gene. This alteration results from a C to T substitution at nucleotide position 770, causing the proline (P) at amino acid position 257 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Breakthrough Genomics, |
RCV001998611 | SCV005190608 | uncertain significance | not provided | criteria provided, single submitter | not provided | ||
| Gene |
RCV001998611 | SCV005401932 | uncertain significance | not provided | 2024-05-14 | criteria provided, single submitter | clinical testing | In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |