ClinVar Miner

Submissions for variant NM_003924.4(PHOX2B):c.222G>T (p.Gln74His)

dbSNP: rs1577561176
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001014823 SCV001175582 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-12 criteria provided, single submitter clinical testing The p.Q74H variant (also known as c.222G>T), located in coding exon 1 of the PHOX2B gene, results from a G to T substitution at nucleotide position 222. The glutamine at codon 74 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003517292 SCV004305255 uncertain significance Haddad syndrome 2023-04-19 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). 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 PHOX2B protein function. ClinVar contains an entry for this variant (Variation ID: 820907). This variant has not been reported in the literature in individuals affected with PHOX2B-related conditions. This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 74 of the PHOX2B protein (p.Gln74His).
Baylor Genetics RCV004569936 SCV005056265 uncertain significance Neuroblastoma, susceptibility to, 2 2023-11-22 criteria provided, single submitter clinical testing

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