Submissions for variant NM_138694.4(PKHD1):c.4141del (p.Val1381fs)

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Total submissions: 4

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000486224	SCV000574374	pathogenic	not provided	2017-03-21	criteria provided, single submitter	clinical testing	The c.4141delG variant in the PKHD1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.4141delG variant causes a frameshift starting with codon Valine 1381, changes this amino acid to a Cysteine residue, and creates a premature Stop codon at position 7 of the new reading frame, denoted p.Val1381CysfsX7. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.4141delG variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.4141delG as a pathogenic variant.
Invitae	RCV000409248	SCV000629916	pathogenic	Autosomal recessive polycystic kidney disease	2024-01-31	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Val1381Cysfs*7) in the PKHD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PKHD1 are known to be pathogenic (PMID: 19940839). This variant is present in population databases (rs778537772, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with PKHD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 371324). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV003470349	SCV004204733	likely pathogenic	Polycystic kidney disease 4	2023-02-01	criteria provided, single submitter	clinical testing
Counsyl	RCV000409248	SCV000486879	likely pathogenic	Autosomal recessive polycystic kidney disease	2016-08-30	no assertion criteria provided	clinical testing

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