. 2021 Nov 4;375:e066288. doi: 10.1136/bmj-2021-066288

Table 2.

Variants identified in patients with definite, probable, and possible non-mitochondrial diagnoses

Family	Age, years	Sex	Contribution	Gene	Variants	ACMG	Inheritance
Definite
40	0	F	Full	ACTA2	NM_001614.4:c.536G >A p.(Arg179His)	P	Monoallelic; de novo
41	42	F	Full	AMACR	NM_014324.6:c.857delT p.(Ile286fs)^*	P	Biallelic
41	42	F	Full	AMACR	NM_014324.6:c.437C >T p.(Pro146Leu)^*	LP	Biallelic
42	57	M	Full	AMACR	NM_014324.6:c.154T >C p.(Ser52Pro); homozygous	P	Biallelic
43	71	F	Full	AMACR	NM_014324.6:c.154T >C p.(Ser52Pro); homozygous	P	Biallelic
44	9	F	Full	AMPD2	NM_001368809.2: c.2228T >C p.(Leu743Pro)^*; homozygous	LP	Biallelic
45	29	M	Full	APP	NM_000484.4:c.2075C >G p.(Ala692Gly)	P	Monoallelic; AD
45	58	F	Full	APP	NM_000484.4:c.2075C >G p.(Ala692Gly)	P	Monoallelic; AD
46	18	M	Partial	ASL	NM_000048.4:c.1153C >T p.(Arg385Cys); homozygous	P	Biallelic
47	15	M	Full	ASXL3	NM_030632.3:c.3464c >A p.(Ser1155Ter)	P	Monoallelic; de novo
48	15	M	Full	ATP1A3	NM_152296.5:c.2452G >A p.(Glu818Lys)	P	Monoallelic; de novo
49	86	F	Full	ATP1A3	NM_152296.5:c.2452G >A p.(Glu818Lys)	P	Monoallelic; unknown
50	5	M	Full	ATP6V1A	NM_001690.4:c.845A >T p.(Asn282Ile)^*	LP	Monoallelic; de novo
51	1	F	Full	ATXN7 ^†	Very large CAG repeat expansion	P	Monoallelic
52	44	F	Full	BBS1	NM_024649.5:c.1169T >G p.(Met390Arg); homozygous	P	Biallelic
53	2	M	Full	BCAP31	NM_001256447.2:c.565C >T p.(Gly189Ter)^*	P	XLR; de novo
54	26	F	Full	C19orf12	NM_001256047.1:c.245dupC p.(Ala83fs)^*	LP	Monoallelic; unknown
55	12	F	Full	CACNA1A	NM_001127221.1:c.4177G >A p.(Val1393Met)	LP	Monoallelic; de novo
56	2	M	Full	CACNA1E	NM_001205293.3:c.683T >C p.(Leu228Pro)	LP	Monoallelic; de novo
57	12	M	Full	CTBP1	NM_001328.3:c.1024C >T p.(Arg342Trp)	P	Monoallelic; de novo
58	11	M	Full	DOCK6	NM_020812.4:c.4106+5G >T	LP	Biallelic
58	10	F	Full	DOCK6	NM_020812.4:c.1902_1905delGTTC p.(Phe635fs)	P	Biallelic
59	12	F	Full	DSP	NM_004415.4:c.1799T >C p.(Phe600Ser)^*	LP	Monoallelic; de novo
60	8	F	Full	EXOSC3	NM_016042.4:c.395A >C p.(Asp132Ala); homozygous	P	Biallelic
61	61	M	Partial	EYA4	NM_004100.5:c.1741A >T p.(Lys581Ter)^*	LP	Monoallelic; unknown
62	2	M	Full	FIG4	NM_014845.6:c.447-2A >G^*	P	Biallelic
62	2	M	Full	FIG4	NM_014845.6:c.827C >T p.(Ser276Phe)^*	LP	Biallelic
63	6	F	Full	GCDH	NM_000159.4:c.1204C >T p.(Arg402Trp)	P	Biallelic
63	6	F	Full	GCDH	NM_000159.4:c.1304C >T p.(Thr435Met)^*	LP	Biallelic
64	3	F	Full	HADHA	NM_000182.5:c.1528G >C p.(Glu510Gln)	P	Biallelic
64	3	F	Full	HADHA	NM_000182.5:c.1664T >G p.(Met555Arg)^*	LP	Biallelic
65	10	F	Full	HK1	NM_000188.3:c.1334C >T p.(Ser445Leu)	P	Monoallelic; de novo
65	8	F	Full	HK1	NM_000188.3:c.1334C >T p.(Ser445Leu)	P	Monoallelic; de novo
66	9	M	Full	HSD17B4	NM_000414.4:c.590_597dupGATCACGG p.(Met200fs)^*	P	Biallelic
66	9	M	Full	HSD17B4	NM_000414.4:c.743G >A p.(Arg248His)^*	LP	Biallelic
67	71	M	Partial	HTT ^†	~40 CAG repeats	P	Monoallelic
68	7	F	Full	HTT ^†	Very large CAG repeat expansion	P	Monoallelic
69	41	M	Partial	KCNQ4	NM_004700.4:c.961G >A p.(Gly321Ser)	P	Monoallelic; unknown
70	6	F	Full	KCNT1	NM_020822.3:c.1885A >c p.(Lys629Gln)	LP	Monoallelic de novo
71	46	F	Full	KIF11	NM_004523.4:c.78-2A >G^*	P	Monoallelic; AD
72	29	M	Partial	KMT2C	NM_170606.3:c.11669delA p.(Gln3890fs)^*	P	Monoallelic; de novo
73	0	F	Full	MBD5	NM_001378120.1 deletion of exon 2	LP	Monoallelic; unknown
74	72	M	Full	MYH2	NM_017534.6:c.2116G >A p.(Glu706Lys)	P	Monoallelic; unknown
75	57	M	Partial	MYH7	NM_000257.4:c.1357C >T p.(Arg453Cys)	P	Monoallelic; unknown
76	13	M	Full	NARS1	NM_004539.4:c.1600C >T p.(Arg534Ter)	P	Monoallelic; de novo
77	19	F	Full	NPHP1	Gene deletion;homozygous	P	Biallelic
77	17	F	Full	NPHP1	Gene deletion;homozygous	P	Biallelic
78	3	M	Full	NPHP1	Gene deletion; homozygous	P	Biallelic
79	31	F	Partial	OPTN	Gene deletion	P	Monoallelic; unknown
80	1	M	Full	P4HTM	NM_177939.3:c.659G >A p.(Trp220Ter)^*	P	Biallelic
80	1	M	Full	P4HTM	NM_177939.3:c.569_579del p.(Gln190fs)^*	P	Biallelic
81	36	F	Full	PDGFB	Gene deletion	P	Monoallelic; AD
82	11	F	Partial	PHKB	NM_000293.3:c.2109delT p.(Ser704fs)^*	P	Biallelic
82	11	F	Partial	PHKB	NM_000293.3:c.2427+977C >T^*	P	Biallelic
83	3	M	Partial	PKD2	NM_000297.4:c.1390C >T p.(Arg464Ter)	P	Monoallelic; AD
84	45	F	Full	PMM2	NM_000303.3:c.442G >A p.(Asp148Asn)	P	Biallelic
				PMM2	NM_000303.3:c.305A >G p.(Tyr102Cys)^*	LP	Biallelic
				AQP2	NM_000486.6:c.707_720dupTGCTGAAGGGCCTG p.(Glu241fs)^*	LP	Biallelic
				AQP2	NM_000486.6:c.34G >A p.(Ala12Thr)^*	LP	Biallelic
85	2	F	Full	POGZ	NM_05100.4:c.2571-2delA^*	P	Monoallelic; de novo
86	54	F	Full	POLR3A	NM_007055.4:c.2119C >T p.(Gln707Ter)	P	Biallelic
86	54	F	Full	POLR3A	NM_007055.4:c.1909+22G >A	P	Biallelic
87	2	M	Full	PPP2R5D	NM_006245.4:c.592G >A p.(Glu198Lys)	P	Monoallelic; de novo
88	7	F	Full	SAMD9	NM_001193307.1: c.2053C >T p.(Arg685Ter)	LP	Monoallelic; de novo
89	24	M	Full	SCN2A	NM_021007.3:c.4480C >A p.(Gln1494Lys)^*	LP	Monoallelic; de novo
90	49	F	Full	SHOC2	NM_007373.4:c.519G >A p.(Met173Ile)	LP	Monoallelic; unknown
91	56	M	Partial	SLC20A2	NM_001257180.2:c.852delC p.(Ile1285fs)^*	LP	Monoallelic; unknown
92	25	M	Full	SLC52A2	NM_001363118.2:c.368T >C p.(Leu123Pro)	P	Biallelic
92	25	M	Full	SLC52A2	NM_001363118.2:c.916G >A p.(Gly306Arg)	P	Biallelic
93	11	F	Full	SOS1	NM_005633.3.3:c.1294T >C p.(Trp432Arg)	P	Monoallelic; de novo
94	12	M	Partial	TAB2	NM_001292034.3: c.-90+1G >C	LP	Monoallelic; de novo
95	7	F	Full	TANGO2	Deletion exons 3-9; homozygous	P	Biallelic
96	58	M	Partial	TTN	NM_001267550.2:c.59926+1G >A	P	Monoallelic unknown
97	73	M	Full	TTR	NM_000371.3:c.407A >C p.(Tyr136Ser)	P	Monoallelic unknown
98	22	F	Full	ZBTB20	NM_001164342.2: c.1916G >A p.(Cys639Tyr)^*	LP	Monoallelic unknown
Probable
99	59	F	Full	CTNNB1	NM_001904.4:c.2315delA p.(Asn772fs)^*	LP	Monoallelic; unknown
100	0	M	Full	MYBPC3	NM_000256.3:c.1357_158delCC p.(Pro453fs)	P	Biallelic
100	0	M	Full	MYBPC3	NM_000256.3:c.1576G >C p.(Ala526Pro)^*	LP	Biallelic
101	22	F	Full	PEX16	NM_057174.2:c.851A >C p.(Tyr284Ser)^*; homozygous	VUS	Biallelic
Possible
102	60	F	Full	MARS1	NM_004990.4:c.493_495delGAG p.(Glu165del)^*	LP	Monoallelic; unknown
103	52	M	Full	MYH2	NM_017534.6:c.2387C >A p.(Ala796Asp)^*	VUS	Monoallelic; unknown
104	13	M	Full	MYO9A	NM_006901.4:c.6796A >T p.(Asn2266Tyr)^*	VUS	Biallelic
104	13	M	Full	MYO9A	NM_006901.4:c.1574A >T p.(Glu525Val)^*	VUS	Biallelic

Genetic diagnoses made in 65 families, including age and sex of participants, contribution to phenotype from this gene (full or partial), gene, variants, American College of Medical Genetics (ACMG) variant classification (P=pathogenic, LP=likely pathogenic, VUS=variant of uncertain clinical significance), and inheritance pattern.

For family 84, full phenotype is explained by two genetic diagnoses. In family 77, NPHP1 homozygous deletion explains phenotype in sibling with severe phenotype (with childhood onset end stage renal disease) and is heterozygous in other sibling.

AD=autosomal dominant; F=female; M=male; XLR=X linked recessive.

Novel variants

^†

Previously published families.