ClinVar Miner

Submissions for variant NM_173630.4(RTTN):c.2255C>T (p.Pro752Leu)

gnomAD frequency: 0.00042  dbSNP: rs35424122
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000500525 SCV000596863 uncertain significance not specified 2016-09-15 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001857159 SCV002227567 uncertain significance not provided 2024-01-25 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 752 of the RTTN protein (p.Pro752Leu). This variant is present in population databases (rs35424122, gnomAD 0.1%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with RTTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 436600). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RTTN protein function. 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.
GeneDx RCV001857159 SCV002818797 uncertain significance not provided 2022-12-23 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002524287 SCV003686362 uncertain significance Inborn genetic diseases 2023-12-11 criteria provided, single submitter clinical testing The c.2255C>T (p.P752L) alteration is located in exon 17 (coding exon 17) of the RTTN gene. This alteration results from a C to T substitution at nucleotide position 2255, causing the proline (P) at amino acid position 752 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GenomeConnect, ClinGen RCV001857159 SCV002818392 not provided not provided no assertion provided phenotyping only Variant classified as "not provided" and reported on 08-27-2021 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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