ClinVar Miner

Submissions for variant NM_003924.4(PHOX2B):c.785G>T (p.Gly262Val)

gnomAD frequency: 0.00001  dbSNP: rs768420488
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001312215 SCV000644052 uncertain significance Haddad syndrome 2023-10-23 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 262 of the PHOX2B protein (p.Gly262Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with congenital central hypoventilation syndrome (PMID: 30672101). ClinVar contains an entry for this variant (Variation ID: 467746). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
Ambry Genetics RCV000561955 SCV000674222 uncertain significance Hereditary cancer-predisposing syndrome 2024-02-12 criteria provided, single submitter clinical testing The p.G262V variant (also known as c.785G>T), located in coding exon 3 of the PHOX2B gene, results from a G to T substitution at nucleotide position 785. The glycine at codon 262 is replaced by valine, an amino acid with dissimilar properties. This alteration has been identified in trans with a polyalanine repeat expansion mutation (PARM) with 24 alanines in a 3 year old diagnosed with congenital central hypoventilation syndrome (Sivan Y et al. Am J Med Genet A, 2019 03;179:503-506). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV000526554 SCV001523106 uncertain significance Congenital central hypoventilation 2019-09-25 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Sema4, Sema4 RCV000561955 SCV002535422 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-14 criteria provided, single submitter curation
GeneDx RCV004592580 SCV005079944 uncertain significance not provided 2023-08-04 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Identified in the heterozygous or homozygous state in individuals with CCHS, both of whom had multiple unaffected relatives also heterozygous for the variant (Sivan et al., 2023); This variant is associated with the following publications: (PMID: 30672101, 37373665, 33958749)
OMIM RCV000526554 SCV001432714 pathogenic Congenital central hypoventilation 2021-08-26 no assertion criteria provided literature only

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