ClinVar Miner

Submissions for variant NM_014714.4(IFT140):c.454C>T (p.Leu152Phe)

gnomAD frequency: 0.00001  dbSNP: rs1403669200
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory of Medical Genetics (UMR_S 1112), INSERM/Strasbourg University RCV000626461 SCV000746988 pathogenic Saldino-Mainzer syndrome 2018-01-01 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV000626461 SCV003443058 likely pathogenic Saldino-Mainzer syndrome 2023-12-21 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 152 of the IFT140 protein (p.Leu152Phe). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with clinical features of asphyxiating thoracic dystrophy and/or Mainzer-Saldino syndrome (PMID: 23418020, 29688594; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 523179). 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 IFT140 protein function with a negative predictive value of 95%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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