ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.3728C>A (p.Thr1243Lys)

gnomAD frequency: 0.00001  dbSNP: rs774865280
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001360680 SCV001556610 uncertain significance Autosomal recessive polycystic kidney disease 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces threonine with lysine at codon 1243 of the PKHD1 protein (p.Thr1243Lys). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and lysine. This variant is present in population databases (rs774865280, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with PKHD1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 RCV002550010 SCV003724163 uncertain significance Inborn genetic diseases 2021-07-20 criteria provided, single submitter clinical testing The c.3728C>A (p.T1243K) alteration is located in exon 32 (coding exon 31) of the PKHD1 gene. This alteration results from a C to A substitution at nucleotide position 3728, causing the threonine (T) at amino acid position 1243 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Laboratory of Gastroenterology and Hepatology, Radboud University Medical Center RCV001844858 SCV001876995 uncertain significance Autosomal dominant polycystic liver disease 2021-09-01 no assertion criteria provided research
Natera, Inc. RCV001360680 SCV002080988 uncertain significance Autosomal recessive polycystic kidney disease 2019-07-05 no assertion criteria provided clinical testing

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