TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27829	83710;83711;83712	chr2:178562647;178562646;178562645	chr2:179427374;179427373;179427372
N2AB	26188	78787;78788;78789	chr2:178562647;178562646;178562645	chr2:179427374;179427373;179427372
N2A	25261	76006;76007;76008	chr2:178562647;178562646;178562645	chr2:179427374;179427373;179427372
N2B	18764	56515;56516;56517	chr2:178562647;178562646;178562645	chr2:179427374;179427373;179427372
Novex-1	18889	56890;56891;56892	chr2:178562647;178562646;178562645	chr2:179427374;179427373;179427372
Novex-2	18956	57091;57092;57093	chr2:178562647;178562646;178562645	chr2:179427374;179427373;179427372
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: Fn3-90
• Domain position: 64
• Structural Position: 96
• Q(SASA): 0.8202
• 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/K	rs374322635	0.467	0.27	N	0.276	0.079	0.119812018005	gnomAD-2.1.1	8.48E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.84E-05	0
N/K	rs374322635	0.467	0.27	N	0.276	0.079	0.119812018005	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
N/K	rs374322635	0.467	0.27	N	0.276	0.079	0.119812018005	gnomAD-4.0.0	1.38009E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80568E-06	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	0.1858	likely_benign	0.1667	benign	-0.165	Destabilizing	0.495	N	0.321	neutral	None	None	None	None	N
N/C	0.2469	likely_benign	0.2454	benign	0.251	Stabilizing	0.995	D	0.396	neutral	None	None	None	None	N
N/D	0.1278	likely_benign	0.126	benign	0.136	Stabilizing	0.001	N	0.177	neutral	N	0.427952798	None	None	N
N/E	0.2943	likely_benign	0.2895	benign	0.078	Stabilizing	0.176	N	0.279	neutral	None	None	None	None	N
N/F	0.5007	ambiguous	0.492	ambiguous	-0.693	Destabilizing	0.981	D	0.438	neutral	None	None	None	None	N
N/G	0.1837	likely_benign	0.1697	benign	-0.281	Destabilizing	0.495	N	0.299	neutral	None	None	None	None	N
N/H	0.1051	likely_benign	0.1096	benign	-0.292	Destabilizing	0.927	D	0.367	neutral	N	0.473001399	None	None	N
N/I	0.2535	likely_benign	0.2457	benign	0.041	Stabilizing	0.927	D	0.453	neutral	N	0.495664785	None	None	N
N/K	0.2323	likely_benign	0.2433	benign	0.147	Stabilizing	0.27	N	0.276	neutral	N	0.475093384	None	None	N
N/L	0.2456	likely_benign	0.2356	benign	0.041	Stabilizing	0.704	D	0.419	neutral	None	None	None	None	N
N/M	0.2757	likely_benign	0.2725	benign	0.211	Stabilizing	0.944	D	0.397	neutral	None	None	None	None	N
N/P	0.4795	ambiguous	0.4122	ambiguous	-0.004	Destabilizing	0.828	D	0.413	neutral	None	None	None	None	N
N/Q	0.2417	likely_benign	0.2399	benign	-0.252	Destabilizing	0.013	N	0.199	neutral	None	None	None	None	N
N/R	0.3219	likely_benign	0.3295	benign	0.221	Stabilizing	0.543	D	0.281	neutral	None	None	None	None	N
N/S	0.1002	likely_benign	0.0969	benign	-0.018	Destabilizing	0.425	N	0.337	neutral	N	0.510206035	None	None	N
N/T	0.1261	likely_benign	0.1221	benign	0.046	Stabilizing	0.425	N	0.264	neutral	N	0.471938216	None	None	N
N/V	0.2466	likely_benign	0.2298	benign	-0.004	Destabilizing	0.828	D	0.457	neutral	None	None	None	None	N
N/W	0.7164	likely_pathogenic	0.7209	pathogenic	-0.772	Destabilizing	0.995	D	0.443	neutral	None	None	None	None	N
N/Y	0.1559	likely_benign	0.1586	benign	-0.466	Destabilizing	0.975	D	0.407	neutral	N	0.495411295	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.