. 2020 Jun 23;15(6):e0235071. doi: 10.1371/journal.pone.0235071

Table 3. Summary of variants identified in the patients.

Patient	Gene	DNA sequence change	Predicted change on protein level	dbSNP ID	Prediction of pathogenity	Inheritance	Clinical diagnosis	Genetic diagnosis	Agreement of clinical and genetic diagnosis
1	*TMEM67*	NM_153704.6:c.1843T>C	p.(Cys615Arg)	rs201893408	Likely Pathogenic	P	ARPKD	NPHP11	No
1	*TMEM67*	NM_153704.6:c.1843T>C	p.(Cys615Arg)	rs201893408	Likely Pathogenic	M	ARPKD	NPHP11	No
2	PKD1	NM_001009944.3:c.6965C>T	p.(Thr2322Met)	rs564570407	--	--	ADPKD–VEO	Unknown	No
	NEK8	NM_178170.3:c.133C>T	p.(Arg45Trp)	rs1567759130	--	--
	COQ8B	NM_024876.4:c.767C>A	p.(Ala256Glu)	rs201827222	--	--
3	*PKHD1* ^a	NM_138694.4:c.5895dupA	p.(Leu1966ThrfsTer4)	rs746838237	Pathogenic	P	ARPKD	ARPKD	Yes
3	*PKHD1* ^a	NM_138694.4:c.8114delG	p.(Gly2705ValfsTer11)	rs774050795	Pathogenic	M	ARPKD	ARPKD	Yes
4	*PKHD1* ^a	NM_138694.4:c.107C>T	p.(Thr36Met)	rs137852944	Likely Pathogenic	M	ARPKD	ARPKD	Yes
4	*PKHD1* ^a	NM_138694.4:c.7561_7568delGCAGCAAT	p.(Ala2521PhefsTer60)	N/A	Pathogenic	--	ARPKD	ARPKD	Yes
5	*PKHD1* ^a	NM_138694.4:c.107C>T	p.(Thr36Met)	rs137852944	Likely Pathogenic	M	ARPKD	ARPKD	Yes
5	*PKHD1* ^a	NM_138694.4:c.10658T>C	p.(Ile3553Thr)	rs137852948		P	ARPKD	ARPKD	Yes
6	*PKHD1* ^a	NM_138694.4:c.8114delG	p.(Gly2705ValfsTer11)	rs774050795	Pathogenic	P	ARPKD	Unknown	No
7	*PKHD1* ^a	NM_138694.4:c.4870C>T	p.(Arg1624Trp)	rs200391019	Uncertain Significance	P	ARPKD	ARPKD	Yes
7	*PKHD1* ^a	NM_138694.4:c.5323C>T	p.(Arg1775Ter)	rs770522674	Pathogenic	M	ARPKD	ARPKD	Yes
8	KIF7	NM_198525.3:c.2227C>T	p.(Gln743Ter)	N/A	--	--	ARPKD	Bilateral blastema nephroblastoma	No
8	GLIS2	NM_032575.2:c.737G>A	p.(Arg246His)	rs770824489	--	--	ARPKD	Bilateral blastema nephroblastoma	No
9	*PKD1*	NM_001009944.3:c.5653dupG	p.(Glu1885GlyfsTer105)	N/A	Pathogenic	M	ADPKD	ADPKD	Yes
10	------						ARPKD, MRKH syndrome	Unknown	No
11	*HNF1B*	whole gene deletion				M	RCAD syndrome	RCAD syndrome	Yes
12	*PKHD1*	NM_138694.4:c.920T>C	p.(Ile307Thr)	rs1288017883	Likely Pathogenic	--	ARPKD	Unknown	No
12	ACTN4	NM_004924.6:c.1279G>A	p.(Ala427Thr)	rs201128110	--	--	ARPKD	Unknown	No
13	*HNF1B*	NM_000458.4:c.523A>T	p.(Lys175Ter)	N/A	Pathogenic	--	RCAD syndrome	RCAD syndrome	Yes
14	*TMEM67*	NM_153704.6:c.1843T>C	p.(Cys615Arg)	rs201893408	Likely Pathogenic	In trans	ARPKD	NPHP11	No
14	*TMEM67*	NM_153704.6:c.1815_1831del	p.(Gln605HisfsTer17)	N/A	Pathogenic	In trans	ARPKD	NPHP11	No
15	*PKHD1*	NM_138694.4:c.107C>T	p.(Thr36Met)	rs137852944	Likely Pathogenic	P	ARPKD	ARPKD	Yes
15	*PKHD1*	NM_138694.4:c.8114delG	p.(Gly2705ValfsTer11)	rs774050795	Pathogenic	--	ARPKD	ARPKD	Yes
16	*PKHD1*	NM_138694.4:c.2725C>T	p.(Arg909Ter)	rs727504089	Pathogenic	--	ARPKD	ARPKD	Yes
16	*PKHD1*	NM_138694.4:c.8870T>C	p.(Ile2957Thr)	rs760222236	Likely Pathogenic	M	ARPKD	ARPKD	Yes
17	*PKHD1*	NM_138694.4:c.4403T>C	p.(Leu1468Pro)	rs140331370	Likely Pathogenic	P	ARPKD	ARPKD	Yes
17	*PKHD1*	NM_138694.4:c.8870T>C	p.(Ile2957Thr)	rs760222236	Likely Pathogenic	M	ARPKD	ARPKD	Yes
18	*PKHD1*	NM_138694.4:c.5323C>T	p.(Arg1775Ter)	rs770522674	Pathogenic	M	ARPKD	ARPKD	Yes
18	*PKHD1*	NM_138694.4:c.5060T>C	p.(Ile1687Thr)	rs794727566	Pathogenic	P	ARPKD	ARPKD	Yes
19	*PKHD1*	NM_138694.4:c.107C>T	p.(Thr36Met)	rs137852944	Likely Pathogenic	M	ARPKD	Unknown	No
19	ZNF423	NM_015069.4:c.1144T>C	p.(Ser322Pro)	rs142835239	Likely Benign	--	ARPKD	Unknown	No
20	*TMEM67*	NM_153704.6:c.1843T>C	p.(Cys615Arg)	rs201893408	Likely Pathogenic	P	ARPKD	NPHP11	No
20	*TMEM67*	NM_153704.6:c.1843T>C	p.(Cys615Arg)	rs201893408	Likely Pathogenic	M	ARPKD	NPHP11	No
21	*PKHD1*	NM_138694.4:c.107C>T	p.(Thr36Met)	rs137852944	Likely Pathogenic	P	ARPKD	ARPKD	Yes
21	*PKHD1*	NM_138694.4:c.9719G>A	p.(Arg3240Gln)	rs146649803	Likely Pathogenic	M	ARPKD	ARPKD	Yes
22	*PKD1*	NM_001009944.3:c.12442G>T	p.(Glu4148Ter)	N/A	Pathogenic	De novo	ADPKD-VEO	ADPKD	Yes
22	PKD1	NM_001009944.3:c.11084A>G	p.(His3695Arg)	N/A	--	M	ADPKD-VEO	ADPKD	Yes
23	*PKHD1*	NM_138694.4:c.664A>G	p.(Ile222Val)	rs369925690	Likely Pathogenic	P	ARPKD	ARPKD	Yes
23	*PKHD1*	NM_138694.4:c.100G>A	p.(Gly34Arg)	N/A	Uncertain Significance	M	ARPKD	ARPKD	Yes
24	*TMEM67*	NM_153704.6:c.1843T>C	p.(Cys615Arg)	rs201893408	Likely Pathogenic	--	ARPKD	NPHP11	No
24	*TMEM67*	NM_153704.6:c.1843T>C	p.(Cys615Arg)	rs201893408	Likely Pathogenic	--	ARPKD	NPHP11	No
25	*BBS1*	NM_024649.5:c.46_47delAG	p.(Ser16GlnfsTer2)	rs1291184039	Pathogenic	P	BBS	BBS	Yes
25	*BBS1*	NM_024649.5:c.1660_1661delAG	p.(Leu555GlnfsTer2)	rs1209299063	Pathogenic	M	BBS	BBS	Yes
26	*PKHD1*	NM_138694.4:c.8870T>C	p.(Ile2957Thr)	rs760222236	Likely Pathogenic	P	ADPKD	Unknown	No
26	TMEM237	NM_001044385.3:c.52C>T	p.(Arg18Ter)	rs199469707	--	M	ADPKD	Unknown	No
27	*PKD1*	NM_001009944.3:c.10619-2A>G		N/A	Pathogenic	de novo	ADPKD	ADPKD	Yes
28	*PKD1*	NM_001009944.3:c.6090delC	p.(Val2031TrpfsTer85)	N/A	Pathogenic	de novo	ARPKD	ADPKD	No
29	*NPHP1*	Deletion of whole gene				--	NPHP	NPHP1	Yes
29	*NPHP1*	Deletion of whole gene				--	NPHP	NPHP1	Yes
30	AGXT	NM_000030.3:c.33dupC	p.(Lys12GlnfsTer156)	rs180177201	--	--	RCAD syndrome	Unknown	No
30	RET	NM_020975.6:c.2372A>T	p.(Tyr791Phe)	rs77724903	--	--	RCAD syndrome	Unknown	No
31	FREM1	NM_144966.5:c.3359A>T	p.(Gln1120Leu)	rs143844459	--	--	ADPKD	Unknown	No
31	FREM1	NM_144966.5:c.3331C>T	p.(His1111Tyr)	rs200339767	--	--	ADPKD	Unknown	No

ADPKD, autosomal dominant polycystic kidney disease; ARPKD, autosomal recessive polycystic kidney disease; BBS, Bardet-Biedl syndrome; M, maternal; MRKH, Mayer-Rokitansky-Kuster-Hauser syndrome; NPHP, nephronophthisis; P, paternal; RCAD, renal cysts and diabetes syndrome; VEO, very early onset.

Pathogenicity predictions was generated by VarSome [24] according to the ACMG guidelines [27]. Additional variants without clear significance on phenotype are in italics.

^a The results were already published in [29]