TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26214	78865;78866;78867	chr2:178567492;178567491;178567490	chr2:179432219;179432218;179432217
N2AB	24573	73942;73943;73944	chr2:178567492;178567491;178567490	chr2:179432219;179432218;179432217
N2A	23646	71161;71162;71163	chr2:178567492;178567491;178567490	chr2:179432219;179432218;179432217
N2B	17149	51670;51671;51672	chr2:178567492;178567491;178567490	chr2:179432219;179432218;179432217
Novex-1	17274	52045;52046;52047	chr2:178567492;178567491;178567490	chr2:179432219;179432218;179432217
Novex-2	17341	52246;52247;52248	chr2:178567492;178567491;178567490	chr2:179432219;179432218;179432217
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-137
• Domain position: 22
• Structural Position: 31
• Q(SASA): 0.6337
• 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/K	rs944710014	-0.119	0.977	N	0.581	0.46	0.378847511475	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.47E-05	0	None	0	0	None	0	None	0	0	0
E/K	rs944710014	-0.119	0.977	N	0.581	0.46	0.378847511475	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	9.65E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs944710014	-0.119	0.977	N	0.581	0.46	0.378847511475	gnomAD-4.0.0	4.33978E-06	None	None	None	None	N	None	8.01218E-05	0	None	0	0	None	0	0	8.47823E-07	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	0.2314	likely_benign	0.2406	benign	-0.487	Destabilizing	0.977	D	0.666	neutral	D	0.534040979	None	None	N
E/C	0.8763	likely_pathogenic	0.8928	pathogenic	-0.432	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
E/D	0.1607	likely_benign	0.1463	benign	-1.351	Destabilizing	0.117	N	0.287	neutral	N	0.459967295	None	None	N
E/F	0.8223	likely_pathogenic	0.8476	pathogenic	0.378	Stabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
E/G	0.3507	ambiguous	0.3558	ambiguous	-0.924	Destabilizing	0.993	D	0.697	prob.neutral	N	0.514436236	None	None	N
E/H	0.618	likely_pathogenic	0.658	pathogenic	-0.03	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
E/I	0.4641	ambiguous	0.4903	ambiguous	0.721	Stabilizing	0.998	D	0.775	deleterious	None	None	None	None	N
E/K	0.3988	ambiguous	0.4475	ambiguous	-0.757	Destabilizing	0.977	D	0.581	neutral	N	0.498600254	None	None	N
E/L	0.5214	ambiguous	0.5409	ambiguous	0.721	Stabilizing	0.998	D	0.771	deleterious	None	None	None	None	N
E/M	0.5687	likely_pathogenic	0.5875	pathogenic	1.088	Stabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
E/N	0.4109	ambiguous	0.4204	ambiguous	-1.312	Destabilizing	0.99	D	0.725	prob.delet.	None	None	None	None	N
E/P	0.8708	likely_pathogenic	0.8665	pathogenic	0.341	Stabilizing	0.998	D	0.803	deleterious	None	None	None	None	N
E/Q	0.2393	likely_benign	0.2598	benign	-1.07	Destabilizing	0.997	D	0.663	neutral	N	0.52022632	None	None	N
E/R	0.5427	ambiguous	0.5901	pathogenic	-0.464	Destabilizing	0.998	D	0.743	deleterious	None	None	None	None	N
E/S	0.3022	likely_benign	0.3152	benign	-1.664	Destabilizing	0.983	D	0.615	neutral	None	None	None	None	N
E/T	0.325	likely_benign	0.3413	ambiguous	-1.292	Destabilizing	0.998	D	0.767	deleterious	None	None	None	None	N
E/V	0.262	likely_benign	0.2752	benign	0.341	Stabilizing	0.997	D	0.773	deleterious	N	0.492964619	None	None	N
E/W	0.93	likely_pathogenic	0.9404	pathogenic	0.567	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/Y	0.7422	likely_pathogenic	0.7776	pathogenic	0.609	Stabilizing	1.0	D	0.767	deleterious	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.