TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35299	106120;106121;106122	chr2:178530720;178530719;178530718	chr2:179395447;179395446;179395445
N2AB	33658	101197;101198;101199	chr2:178530720;178530719;178530718	chr2:179395447;179395446;179395445
N2A	32731	98416;98417;98418	chr2:178530720;178530719;178530718	chr2:179395447;179395446;179395445
N2B	26234	78925;78926;78927	chr2:178530720;178530719;178530718	chr2:179395447;179395446;179395445
Novex-1	26359	79300;79301;79302	chr2:178530720;178530719;178530718	chr2:179395447;179395446;179395445
Novex-2	26426	79501;79502;79503	chr2:178530720;178530719;178530718	chr2:179395447;179395446;179395445
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-165
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.3812
• 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
E/D	rs886055219	None	None	N	0.071	0.084	0.0297737177859	gnomAD-4.0.0	8.20981E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.07928E-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
E/A	0.1778	likely_benign	0.1817	benign	-0.046	Destabilizing	None	N	0.114	neutral	N	0.479383617	None	None	N
E/C	0.8692	likely_pathogenic	0.8653	pathogenic	-0.331	Destabilizing	0.049	N	0.401	neutral	None	None	None	None	N
E/D	0.056	likely_benign	0.0586	benign	-0.426	Destabilizing	None	N	0.071	neutral	N	0.409771603	None	None	N
E/F	0.7843	likely_pathogenic	0.7898	pathogenic	-0.071	Destabilizing	0.021	N	0.347	neutral	None	None	None	None	N
E/G	0.0947	likely_benign	0.0964	benign	-0.149	Destabilizing	None	N	0.117	neutral	N	0.459064273	None	None	N
E/H	0.4862	ambiguous	0.4973	ambiguous	0.598	Stabilizing	0.017	N	0.285	neutral	None	None	None	None	N
E/I	0.5177	ambiguous	0.5092	ambiguous	0.169	Stabilizing	0.003	N	0.335	neutral	None	None	None	None	N
E/K	0.1978	likely_benign	0.1991	benign	0.331	Stabilizing	None	N	0.166	neutral	N	0.444038892	None	None	N
E/L	0.5417	ambiguous	0.5433	ambiguous	0.169	Stabilizing	0.001	N	0.294	neutral	None	None	None	None	N
E/M	0.5772	likely_pathogenic	0.5887	pathogenic	-0.103	Destabilizing	0.049	N	0.414	neutral	None	None	None	None	N
E/N	0.1177	likely_benign	0.1256	benign	0.03	Stabilizing	None	N	0.139	neutral	None	None	None	None	N
E/P	0.6371	likely_pathogenic	0.6403	pathogenic	0.114	Stabilizing	0.001	N	0.289	neutral	None	None	None	None	N
E/Q	0.1977	likely_benign	0.2082	benign	0.043	Stabilizing	0.001	N	0.276	neutral	N	0.425567775	None	None	N
E/R	0.3408	ambiguous	0.3398	benign	0.59	Stabilizing	0.001	N	0.238	neutral	None	None	None	None	N
E/S	0.1652	likely_benign	0.1748	benign	-0.083	Destabilizing	None	N	0.105	neutral	None	None	None	None	N
E/T	0.2311	likely_benign	0.2399	benign	0.013	Stabilizing	None	N	0.184	neutral	None	None	None	None	N
E/V	0.331	likely_benign	0.3191	benign	0.114	Stabilizing	None	N	0.229	neutral	N	0.443399713	None	None	N
E/W	0.8978	likely_pathogenic	0.8972	pathogenic	-0.025	Destabilizing	0.152	N	0.324	neutral	None	None	None	None	N
E/Y	0.5799	likely_pathogenic	0.5717	pathogenic	0.145	Stabilizing	0.021	N	0.338	neutral	None	None	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.