Submissions for variant NM_138694.4(PKHD1):c.10926G>A (p.Met3642Ile)

gnomAD frequency: 0.00076  dbSNP: rs78518523

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000723889	SCV000203259	uncertain significance	not provided	2018-04-27	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000153701	SCV000596428	uncertain significance	not specified	2016-08-23	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001164890	SCV001327049	uncertain significance	Autosomal recessive polycystic kidney disease	2017-04-27	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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Invitae	RCV001164890	SCV001415551	likely benign	Autosomal recessive polycystic kidney disease	2024-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000723889	SCV001765900	uncertain significance	not provided	2022-10-19	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 26489027, 16523049, 20981092, 15805161, 20413436, 19914852)
Myriad Genetics, Inc.	RCV001810428	SCV002060078	uncertain significance	Polycystic kidney disease 4	2021-11-19	criteria provided, single submitter	clinical testing	NM_138694.3(PKHD1):c.10926G>A(M3642I) is a missense variant classified as a variant of uncertain significance in the context of autosomal recessive polycystic kidney disease, PKHD1-related. M3642I has been observed in cases with relevant disease (PMID: 19914852, 16523049, 15805161). Functional assessments of this variant are not available in the literature. M3642I has been observed in population frequency databases (gnomAD: NFE 0.13%). In summary, there is insufficient evidence to classify NM_138694.3(PKHD1):c.10926G>A(M3642I) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening.
Mendelics	RCV000153701	SCV002519135	uncertain significance	not specified	2022-05-04	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003945211	SCV004759135	uncertain significance	PKHD1-related condition	2024-02-07	criteria provided, single submitter	clinical testing	The PKHD1 c.10926G>A variant is predicted to result in the amino acid substitution p.Met3642Ile. This variant was reported in individuals with polycystic kidney disease, but the pathogenicity has not been conclusively established (Sharp et al. 2005. PubMed ID: 15805161; Gunay-Aygun et al. 2010. PubMed ID: 19914852; Nicolaou et al. 2016. PubMed ID: 26489027, Supplementary Table 5). This variant is reported in 0.13% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000723889	SCV001551117	uncertain significance	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001164890	SCV002075495	uncertain significance	Autosomal recessive polycystic kidney disease	2017-11-17	no assertion criteria provided	clinical testing