ClinVar Miner

Submissions for variant NM_015466.4(PTPN23):c.3748G>A (p.Glu1250Lys)

gnomAD frequency: 0.00011  dbSNP: rs148689441
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001856217 SCV002186569 uncertain significance not provided 2022-08-16 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1250 of the PTPN23 protein (p.Glu1250Lys). This variant is present in population databases (rs148689441, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of PTPN23-related conditions (PMID: 31395947). ClinVar contains an entry for this variant (Variation ID: 636315). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 RCV004027360 SCV004935254 uncertain significance Inborn genetic diseases 2024-03-14 criteria provided, single submitter clinical testing The c.3748G>A (p.E1250K) alteration is located in exon 20 (coding exon 20) of the PTPN23 gene. This alteration results from a G to A substitution at nucleotide position 3748, causing the glutamic acid (E) at amino acid position 1250 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Regeneron Genetics Center, Regeneron RCV000853202 SCV000927109 likely pathogenic Global developmental delay; Brain atrophy 2019-02-15 no assertion criteria provided research Identified in cohort of patients with neurodevelopmental disorder accompanied by structural brain abnormalities

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