TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16958	51097;51098;51099	chr2:178611257;178611256;178611255	chr2:179475984;179475983;179475982
N2AB	15317	46174;46175;46176	chr2:178611257;178611256;178611255	chr2:179475984;179475983;179475982
N2A	14390	43393;43394;43395	chr2:178611257;178611256;178611255	chr2:179475984;179475983;179475982
N2B	7893	23902;23903;23904	chr2:178611257;178611256;178611255	chr2:179475984;179475983;179475982
Novex-1	8018	24277;24278;24279	chr2:178611257;178611256;178611255	chr2:179475984;179475983;179475982
Novex-2	8085	24478;24479;24480	chr2:178611257;178611256;178611255	chr2:179475984;179475983;179475982
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-111
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.297
• 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
D/E	None	None	0.004	N	0.229	0.045	0.134241683229	gnomAD-4.0.0	1.59477E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43592E-05	0
D/V	None	None	0.83	N	0.798	0.446	0.301455362545	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

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
D/A	0.2431	likely_benign	0.1939	benign	-0.11	Destabilizing	0.41	N	0.655	neutral	N	0.456015178	None	None	N
D/C	0.697	likely_pathogenic	0.6063	pathogenic	-0.019	Destabilizing	0.993	D	0.801	deleterious	None	None	None	None	N
D/E	0.2278	likely_benign	0.1586	benign	-0.322	Destabilizing	0.004	N	0.229	neutral	N	0.446097099	None	None	N
D/F	0.6305	likely_pathogenic	0.5483	ambiguous	0.031	Stabilizing	0.993	D	0.827	deleterious	None	None	None	None	N
D/G	0.3495	ambiguous	0.2686	benign	-0.324	Destabilizing	0.581	D	0.652	neutral	N	0.508562755	None	None	N
D/H	0.3761	ambiguous	0.3001	benign	0.2	Stabilizing	0.974	D	0.785	deleterious	N	0.508562755	None	None	N
D/I	0.3604	ambiguous	0.2913	benign	0.407	Stabilizing	0.929	D	0.82	deleterious	None	None	None	None	N
D/K	0.5346	ambiguous	0.428	ambiguous	0.347	Stabilizing	0.764	D	0.72	prob.delet.	None	None	None	None	N
D/L	0.4003	ambiguous	0.3135	benign	0.407	Stabilizing	0.866	D	0.795	deleterious	None	None	None	None	N
D/M	0.6559	likely_pathogenic	0.576	pathogenic	0.378	Stabilizing	0.993	D	0.808	deleterious	None	None	None	None	N
D/N	0.1294	likely_benign	0.1173	benign	-0.01	Destabilizing	0.83	D	0.705	prob.neutral	N	0.477108587	None	None	N
D/P	0.8622	likely_pathogenic	0.8216	pathogenic	0.258	Stabilizing	0.929	D	0.785	deleterious	None	None	None	None	N
D/Q	0.427	ambiguous	0.3362	benign	0.044	Stabilizing	0.764	D	0.776	deleterious	None	None	None	None	N
D/R	0.5552	ambiguous	0.4593	ambiguous	0.539	Stabilizing	0.764	D	0.779	deleterious	None	None	None	None	N
D/S	0.1816	likely_benign	0.152	benign	-0.1	Destabilizing	0.48	N	0.586	neutral	None	None	None	None	N
D/T	0.3086	likely_benign	0.247	benign	0.07	Stabilizing	0.866	D	0.725	prob.delet.	None	None	None	None	N
D/V	0.2238	likely_benign	0.1762	benign	0.258	Stabilizing	0.83	D	0.798	deleterious	N	0.439630128	None	None	N
D/W	0.9165	likely_pathogenic	0.882	pathogenic	0.152	Stabilizing	0.993	D	0.821	deleterious	None	None	None	None	N
D/Y	0.3132	likely_benign	0.2532	benign	0.273	Stabilizing	0.991	D	0.828	deleterious	D	0.570023803	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.