ClinVar Miner

Submissions for variant NM_001009944.3(PKD1):c.4055G>A (p.Ser1352Asn) (rs141274774)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000436538 SCV000520767 uncertain significance not specified 2016-12-16 criteria provided, single submitter clinical testing The S1352N variant in the PKD1 gene has been reported previously as in an individual with autosomal dominant polycystic kidney disease who was also heterozygous for two other missense variants in PKD1 (Eisenberger et al., 2015); no additional clinical or family history was provided for this individual. Although not present in the homozygous state, the NHLBI ESP Exome Sequencing Project reports S1352N was observed with a frequency of 0.13% (11/8592 alleles) from individuals of European American background, indicating it may be a rare (benign) variant in this population. The S1352N variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Given the available evidence, we interpret S1352N as a variant of uncertain significance.
Athena Diagnostics Inc RCV000992579 SCV001144980 likely benign not provided 2018-12-07 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001002136 SCV001159991 uncertain significance Polycystic kidney disease, adult type 2019-03-15 criteria provided, single submitter clinical testing The PKD1 c.4055G>A; p.Ser1352Asn variant (rs141274774) is reported in the literature in several individuals affected with autosomal dominant polycystic kidney disease, although its clinical significance was not conclusively determined (Eisenberger 2015, Rossetti 2007). This variant is found in the non-Finnish European population with an overall allele frequency of 0.13% (162/126792 alleles) in the Genome Aggregation Database. The serine at codon 1352 is moderately conserved and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. However, due to limited information, the clinical significance of the p.Ser1352Asn variant is uncertain at this time. References: Eisenberger T et al. An efficient and comprehensive strategy for genetic diagnostics of polycystic kidney disease. PLoS One. 2015 Feb 3;10(2):e0116680. Rossetti S et al. Comprehensive molecular diagnostics in autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 2007 Jul;18(7):2143-60.

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