Submissions for variant NM_033310.3(KCNK4):c.698C>T (p.Pro233Leu)

dbSNP: rs2034823903

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001261924	SCV001367178	uncertain significance	Facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth syndrome	2020-03-25	criteria provided, single submitter	clinical testing	This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PM2.
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology	RCV001261924	SCV001439267	likely pathogenic	Facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth syndrome	2019-12-19	criteria provided, single submitter	research	ACMG codes:PS2, PM2, PP3
Labcorp Genetics (formerly Invitae), Labcorp	RCV001863109	SCV002297060	uncertain significance	not provided	2024-05-15	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 233 of the KCNK4 protein (p.Pro233Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with KCNK4-related conditions. ClinVar contains an entry for this variant (Variation ID: 930709). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Revvity Omics, Revvity	RCV001261924	SCV003814031	uncertain significance	Facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth syndrome	2021-09-08	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV001261924	SCV004697868	likely pathogenic	Facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth syndrome	2024-02-16	criteria provided, single submitter	clinical testing	Criteria applied: PS2,PS4_MOD,PM2_SUP