Submissions for variant NM_138694.4(PKHD1):c.1913T>C (p.Met638Thr)

gnomAD frequency: 0.00003  dbSNP: rs181546197

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000592067	SCV000702214	uncertain significance	not provided	2018-05-08	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001163765	SCV001325836	uncertain significance	Autosomal recessive polycystic kidney disease	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae	RCV001163765	SCV002381260	likely benign	Autosomal recessive polycystic kidney disease	2024-01-25	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV003133389	SCV003808424	uncertain significance	Polycystic kidney disease 4	2021-05-03	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003905514	SCV004727672	likely benign	PKHD1-related disorder	2022-12-22	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Ambry Genetics	RCV004024712	SCV005006782	uncertain significance	Inborn genetic diseases	2023-12-09	criteria provided, single submitter	clinical testing	The c.1913T>C (p.M638T) alteration is located in exon 20 (coding exon 19) of the PKHD1 gene. This alteration results from a T to C substitution at nucleotide position 1913, causing the methionine (M) at amino acid position 638 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.