ClinVar Miner

Submissions for variant NM_006767.4(LZTR1):c.677C>T (p.Pro226Leu)

dbSNP: rs2147964011
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001916004 SCV002183666 uncertain significance not provided 2022-10-05 criteria provided, single submitter clinical testing 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. 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 LZTR1 protein function. ClinVar contains an entry for this variant (Variation ID: 1406808). This variant has not been reported in the literature in individuals affected with LZTR1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 226 of the LZTR1 protein (p.Pro226Leu).
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego RCV004545835 SCV004046289 likely pathogenic LZTR1-related disorder criteria provided, single submitter clinical testing This variant has been previously reported as a heterozygous change in an individual with growth hormone deficiency (PMID: 34826401). It is absent from the gnomAD population database and thus presumed to be rare. The c.677C>T (p.Pro226Leu) variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, the c.677C>T (p.Pro226Leu) variant is classified as Likely Pathogenic.

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