ClinVar Miner

Submissions for variant NM_005055.5(RAPSN):c.41T>C (p.Leu14Pro)

gnomAD frequency: 0.00001  dbSNP: rs104894300
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001851738 SCV002238650 pathogenic Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 11 2023-08-07 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects RAPSN function (PMID: 11791205). 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 RAPSN protein function. ClinVar contains an entry for this variant (Variation ID: 8047). This missense change has been observed in individual(s) with RAPSN-related conditions (PMID: 11791205, 12730725, 19620612). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs104894300, gnomAD 0.002%). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 14 of the RAPSN protein (p.Leu14Pro).
Baylor Genetics RCV003460439 SCV004206098 likely pathogenic Fetal akinesia deformation sequence 2 2024-01-03 criteria provided, single submitter clinical testing
GeneDx RCV004719634 SCV005324900 pathogenic not provided 2024-02-08 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect (PMID: 11791205); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 36815443, 34033754, 31998752, 31549961, 18567858, 12651869, 16945936, 36608736, 22678886, 11791205, 12730725, 12929188, 14504330, 19620612)
OMIM RCV000008513 SCV000028721 pathogenic Congenital myasthenic syndrome 11 2003-01-01 no assertion criteria provided literature only

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