ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.10973T>C (p.Ile3658Thr)

gnomAD frequency: 0.00016  dbSNP: rs142536551
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000460905 SCV000545852 uncertain significance Autosomal recessive polycystic kidney disease 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 3658 of the PKHD1 protein (p.Ile3658Thr). The isoleucine residue is weakly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs142536551, ExAC 0.06%). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
Eurofins Ntd Llc (ga) RCV000733283 SCV000861329 uncertain significance not provided 2018-05-30 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000460905 SCV001327048 uncertain significance Autosomal recessive polycystic kidney disease 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Fulgent Genetics, Fulgent Genetics RCV002489027 SCV002782792 uncertain significance Polycystic kidney disease 4 2022-05-31 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003409618 SCV004114705 uncertain significance PKHD1-related condition 2022-09-01 criteria provided, single submitter clinical testing The PKHD1 c.10973T>C variant is predicted to result in the amino acid substitution p.Ile3658Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.044% of alleles in individuals of European (Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-51523951-A-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Natera, Inc. RCV000460905 SCV002075494 uncertain significance Autosomal recessive polycystic kidney disease 2017-11-20 no assertion criteria provided clinical testing

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