TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17614	53065;53066;53067	chr2:178607947;178607946;178607945	chr2:179472674;179472673;179472672
N2AB	15973	48142;48143;48144	chr2:178607947;178607946;178607945	chr2:179472674;179472673;179472672
N2A	15046	45361;45362;45363	chr2:178607947;178607946;178607945	chr2:179472674;179472673;179472672
N2B	8549	25870;25871;25872	chr2:178607947;178607946;178607945	chr2:179472674;179472673;179472672
Novex-1	8674	26245;26246;26247	chr2:178607947;178607946;178607945	chr2:179472674;179472673;179472672
Novex-2	8741	26446;26447;26448	chr2:178607947;178607946;178607945	chr2:179472674;179472673;179472672
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-16
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.737
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
N/D	None	None	0.801	N	0.271	0.199	0.16115917748	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
N/S	rs1162109348	0.235	0.136	N	0.137	0.17	0.128392430309	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
N/S	rs1162109348	0.235	0.136	N	0.137	0.17	0.128392430309	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
N/S	rs1162109348	0.235	0.136	N	0.137	0.17	0.128392430309	gnomAD-4.0.0	6.5825E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47241E-05	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
N/A	0.137	likely_benign	0.1271	benign	-0.091	Destabilizing	0.525	D	0.263	neutral	None	None	None	None	N
N/C	0.3064	likely_benign	0.2757	benign	0.108	Stabilizing	0.998	D	0.236	neutral	None	None	None	None	N
N/D	0.0994	likely_benign	0.0918	benign	-0.004	Destabilizing	0.801	D	0.271	neutral	N	0.418896171	None	None	N
N/E	0.1918	likely_benign	0.1745	benign	-0.074	Destabilizing	0.525	D	0.261	neutral	None	None	None	None	N
N/F	0.5408	ambiguous	0.5034	ambiguous	-0.72	Destabilizing	0.974	D	0.23	neutral	None	None	None	None	N
N/G	0.1767	likely_benign	0.1583	benign	-0.161	Destabilizing	0.688	D	0.267	neutral	None	None	None	None	N
N/H	0.1121	likely_benign	0.1033	benign	-0.179	Destabilizing	0.028	N	0.162	neutral	N	0.466380687	None	None	N
N/I	0.2277	likely_benign	0.2288	benign	-0.006	Destabilizing	0.966	D	0.246	neutral	N	0.469978353	None	None	N
N/K	0.1335	likely_benign	0.1281	benign	0.068	Stabilizing	0.002	N	0.083	neutral	N	0.384628882	None	None	N
N/L	0.1968	likely_benign	0.1972	benign	-0.006	Destabilizing	0.842	D	0.259	neutral	None	None	None	None	N
N/M	0.2795	likely_benign	0.2669	benign	0.067	Stabilizing	0.991	D	0.209	neutral	None	None	None	None	N
N/P	0.3295	likely_benign	0.3286	benign	-0.013	Destabilizing	0.974	D	0.248	neutral	None	None	None	None	N
N/Q	0.2041	likely_benign	0.1863	benign	-0.261	Destabilizing	0.842	D	0.207	neutral	None	None	None	None	N
N/R	0.1807	likely_benign	0.1684	benign	0.151	Stabilizing	0.728	D	0.223	neutral	None	None	None	None	N
N/S	0.067	likely_benign	0.0664	benign	-0.039	Destabilizing	0.136	N	0.137	neutral	N	0.41354628	None	None	N
N/T	0.0938	likely_benign	0.0961	benign	-0.009	Destabilizing	0.669	D	0.243	neutral	N	0.439135371	None	None	N
N/V	0.1891	likely_benign	0.1899	benign	-0.013	Destabilizing	0.915	D	0.261	neutral	None	None	None	None	N
N/W	0.6853	likely_pathogenic	0.6426	pathogenic	-0.871	Destabilizing	0.998	D	0.324	neutral	None	None	None	None	N
N/Y	0.1968	likely_benign	0.188	benign	-0.545	Destabilizing	0.934	D	0.233	neutral	N	0.457414487	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.