Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV001329478 | SCV001520931 | uncertain significance | Polycystic kidney disease, adult type | 2020-02-12 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Gene |
RCV002285471 | SCV002575823 | uncertain significance | not provided | 2022-03-23 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV003263928 | SCV003948122 | uncertain significance | Inborn genetic diseases | 2023-03-24 | criteria provided, single submitter | clinical testing | The c.8002C>G (p.L2668V) alteration is located in exon 21 (coding exon 21) of the PKD1 gene. This alteration results from a C to G substitution at nucleotide position 8002, causing the leucine (L) at amino acid position 2668 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Victorian Clinical Genetics Services, |
RCV001329478 | SCV005398813 | uncertain significance | Polycystic kidney disease, adult type | 2024-10-10 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.5, this variant is classified as VUS-3C. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with polycystic kidney disease 1 (MIM#173900). (I) 0107 - This gene is associated with autosomal dominant disease. Polycystic kidney disease 1 (MIM#173900) is predominantly caused by monoallelic variants, with rare reports of biallelic variants causing disease (OMIM). (I) 0200 - Variant is predicted to result in a missense amino acid change from leucine to valine. (I) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v4) <0.001 for a dominant condition (34 heterozygotes, 0 homozygote). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0703 - Other missense variants comparable to the one identified in this case have moderate previous evidence for pathogenicity. p.(Leu2668Pro) has been identified in multiple affected families (PMIDs: 29529603, 24611717). (SP) 0809 - Previous evidence of pathogenicity for this variant is inconclusive. There are multiple VUS reports in ClinVar. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Department of Pathology and Laboratory Medicine, |
RCV001292281 | SCV001480991 | uncertain significance | Polycystic kidney disease | no assertion criteria provided | clinical testing | PKD1, EXON21, c.8002C>G, p.Leu2668Val, Heterozygous, Uncertain SignificancernThe PKD1 p.Leu2668Val variant was not identified in the literature nor was it identified in the following databases: ClinVar, LOVD 3.0, ADPKD Mutation Database, or PKD1-LOVD. The variant was identified in dbSNP (ID: rs761726794) and in control databases in 6 of 253132 chromosomes at a frequency of 0.00002 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European in 4 of 118566 chromosomes (freq: 0.00003) and South Asian in 2 of 30312 chromosomes (freq: 0.00007), but not in the African, Other, Latino, Ashkenazi Jewish, East Asian, or Finnish populations. The p.Leu2668 residue is conserved in mammals but not in more distantly related organisms, although four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and 1 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predicts a greater than 10% difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. Assessment Date: 2019/06/26 |