Submissions for variant NM_001080414.4(CCDC88C):c.6026C>T (p.Pro2009Leu)

gnomAD frequency: 0.00078  dbSNP: rs201940261

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000513515	SCV000608711	uncertain significance	not provided	2023-10-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000765186	SCV000896421	uncertain significance	Hydrocephalus, nonsyndromic, autosomal recessive 1; Spinocerebellar ataxia type 40	2018-10-31	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000513515	SCV003248858	uncertain significance	not provided	2024-11-11	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 2009 of the CCDC88C protein (p.Pro2009Leu). This variant is present in population databases (rs201940261, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with CCDC88C-related conditions. ClinVar contains an entry for this variant (Variation ID: 444336). 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.
Ambry Genetics	RCV002524960	SCV003567887	uncertain significance	Inborn genetic diseases	2022-05-31	criteria provided, single submitter	clinical testing	The c.6026C>T (p.P2009L) alteration is located in exon 30 (coding exon 30) of the CCDC88C gene. This alteration results from a C to T substitution at nucleotide position 6026, causing the proline (P) at amino acid position 2009 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx	RCV000513515	SCV005327958	uncertain significance	not provided	2023-06-14	criteria provided, single submitter	clinical testing	Reported in the heterozygous state in a patient with cerebellar ataxia (Ghorbani et al., 2022); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 35401678)
O&I group, Department of Genetics, University Medical Center of Groningen	RCV001849184	SCV001960866	uncertain significance	Spinocerebellar ataxia type 40	2021-07-22	no assertion criteria provided	research
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000513515	SCV001963179	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000513515	SCV001965933	uncertain significance	not provided		no assertion criteria provided	clinical testing