ClinVar Miner

Submissions for variant NM_001184880.2(PCDH19):c.1671C>G (p.Asn557Lys)

dbSNP: rs267606933
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV000011769 SCV002557271 likely pathogenic Developmental and epileptic encephalopathy, 9 2024-10-10 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.2, this variant is classified as Likely Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene. (I) 0110 - This gene is associated with X-linked disease primarily affecting heterozygous females, however, mosaic males have also been reported less frequently (PMID: 30287595) (I) 0200 - Variant is predicted to result in a missense amino acid change from asparagine to lysine (exon 1). (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools and highly conserved with a moderate amino acid change. (SP) 0601 - Variant is located in the extracellular domain where most missense variants have been reported ((PMID: 18469813, 23334464). (SP) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0803 - This variant has limited previous evidence of pathogenicity in one individual. The variant has been previously reported in female patient with epilepsy and mental retardation limited to females (this patient) (ClinVar, PMID: 18469813). (SP) 1001 - This variant has strong functional evidence supporting abnormal protein function. Functional studies show that this variant causes reduced transcriptional activity and premature differentiation of human neural stem and progenitor cells. (ClinVar, PMID: 28334947, 29763708). (SP) 1206 - This variant has been shown to be paternally inherited (research lab result). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
OMIM RCV000011769 SCV000032001 pathogenic Developmental and epileptic encephalopathy, 9 2010-03-01 no assertion criteria provided literature only

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