ClinVar Miner

Submissions for variant NM_000944.5(PPP3CA):c.1265C>T (p.Thr422Met)

gnomAD frequency: 0.00001  dbSNP: rs745416220
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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 RCV002028135 SCV002269888 uncertain significance not provided 2024-07-31 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 422 of the PPP3CA protein (p.Thr422Met). 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 variant has not been reported in the literature in individuals affected with PPP3CA-related conditions. ClinVar contains an entry for this variant (Variation ID: 1483821). 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 PPP3CA protein function with a negative predictive value of 80%. 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.
Fulgent Genetics, Fulgent Genetics RCV002497958 SCV002777903 uncertain significance Developmental and epileptic encephalopathy 91; Arthrogryposis, cleft palate, craniosynostosis, and impaired intellectual development 2022-04-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV002579604 SCV003535966 uncertain significance Inborn genetic diseases 2022-03-07 criteria provided, single submitter clinical testing The c.1265C>T (p.T422M) alteration is located in exon 12 (coding exon 12) of the PPP3CA gene. This alteration results from a C to T substitution at nucleotide position 1265, causing the threonine (T) at amino acid position 422 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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