ClinVar Miner

Submissions for variant NM_000557.5(GDF5):c.1322T>C (p.Leu441Pro)

gnomAD frequency: 0.00001  dbSNP: rs28936683
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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 RCV003555978 SCV004298064 pathogenic not provided 2023-09-27 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 441 of the GDF5 protein (p.Leu441Pro). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects GDF5 function (PMID: 16127465, 21976273). 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 expected to disrupt GDF5 protein function. ClinVar contains an entry for this variant (Variation ID: 8381). This variant is also known as L60P. This missense change has been observed in individuals with GDF5-related conditions (PMID: 12121354, 16014698). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency).
OMIM RCV000008887 SCV000029097 pathogenic Acromesomelic dysplasia 2B 2006-03-01 no assertion criteria provided literature only
OMIM RCV000008888 SCV000029098 pathogenic Type A2 brachydactyly 2006-03-01 no assertion criteria provided literature only
Clinical Genetics Laboratory, University Hospital Schleswig-Holstein RCV001770033 SCV002011717 likely pathogenic Symphalangism, proximal, 1B 2021-09-23 no assertion criteria provided clinical testing

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