ClinVar Miner

Submissions for variant NM_003924.4(PHOX2B):c.694C>A (p.Pro232Thr)

dbSNP: rs1433654836
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000566769 SCV000674220 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-04 criteria provided, single submitter clinical testing The p.P232T variant (also known as c.694C>A), located in coding exon 3 of the PHOX2B gene, results from a C to A substitution at nucleotide position 694. The proline at codon 232 is replaced by threonine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000686141 SCV000813645 uncertain significance Haddad syndrome 2023-07-10 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 232 of the PHOX2B protein (p.Pro232Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PHOX2B-related conditions. ClinVar contains an entry for this variant (Variation ID: 486033). 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 PHOX2B 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.
Baylor Genetics RCV004569282 SCV005055332 uncertain significance Neuroblastoma, susceptibility to, 2 2023-12-02 criteria provided, single submitter clinical testing
GeneDx RCV004767407 SCV005379816 uncertain significance not provided 2023-11-29 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV005034140 SCV005665281 uncertain significance Neuroblastoma, susceptibility to, 2; Central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease 2024-04-29 criteria provided, single submitter clinical testing

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