TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28137	84634;84635;84636	chr2:178561723;178561722;178561721	chr2:179426450;179426449;179426448
N2AB	26496	79711;79712;79713	chr2:178561723;178561722;178561721	chr2:179426450;179426449;179426448
N2A	25569	76930;76931;76932	chr2:178561723;178561722;178561721	chr2:179426450;179426449;179426448
N2B	19072	57439;57440;57441	chr2:178561723;178561722;178561721	chr2:179426450;179426449;179426448
Novex-1	19197	57814;57815;57816	chr2:178561723;178561722;178561721	chr2:179426450;179426449;179426448
Novex-2	19264	58015;58016;58017	chr2:178561723;178561722;178561721	chr2:179426450;179426449;179426448
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-92
• Domain position: 83
• Structural Position: 117
• Q(SASA): 0.273
• Predicted PPI site: I

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
K/E	None	None	0.124	N	0.585	0.123	0.199424873507	gnomAD-4.0.0	2.04055E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.23125E-05	0	0
K/M	None	None	0.958	N	0.72	0.299	0.326616659874	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
K/A	0.488	ambiguous	0.4525	ambiguous	-0.531	Destabilizing	0.272	N	0.609	neutral	None	None	None	None	I
K/C	0.7086	likely_pathogenic	0.6366	pathogenic	-0.529	Destabilizing	0.968	D	0.824	deleterious	None	None	None	None	I
K/D	0.8278	likely_pathogenic	0.8073	pathogenic	-0.058	Destabilizing	0.567	D	0.672	neutral	None	None	None	None	I
K/E	0.2757	likely_benign	0.2722	benign	0.023	Stabilizing	0.124	N	0.585	neutral	N	0.482307358	None	None	I
K/F	0.7852	likely_pathogenic	0.7407	pathogenic	-0.342	Destabilizing	0.726	D	0.8	deleterious	None	None	None	None	I
K/G	0.6887	likely_pathogenic	0.6256	pathogenic	-0.862	Destabilizing	0.272	N	0.7	prob.neutral	None	None	None	None	I
K/H	0.4344	ambiguous	0.3942	ambiguous	-1.168	Destabilizing	0.006	N	0.473	neutral	None	None	None	None	I
K/I	0.275	likely_benign	0.2688	benign	0.309	Stabilizing	0.726	D	0.802	deleterious	None	None	None	None	I
K/L	0.3716	ambiguous	0.3437	ambiguous	0.309	Stabilizing	0.272	N	0.711	prob.delet.	None	None	None	None	I
K/M	0.2418	likely_benign	0.2358	benign	0.261	Stabilizing	0.958	D	0.72	prob.delet.	N	0.500781262	None	None	I
K/N	0.605	likely_pathogenic	0.574	pathogenic	-0.305	Destabilizing	0.22	N	0.643	neutral	N	0.521673823	None	None	I
K/P	0.7299	likely_pathogenic	0.6853	pathogenic	0.06	Stabilizing	0.726	D	0.723	prob.delet.	None	None	None	None	I
K/Q	0.1629	likely_benign	0.1533	benign	-0.445	Destabilizing	0.331	N	0.669	neutral	N	0.466801975	None	None	I
K/R	0.0843	likely_benign	0.0801	benign	-0.476	Destabilizing	0.001	N	0.225	neutral	N	0.451429877	None	None	I
K/S	0.5941	likely_pathogenic	0.5519	ambiguous	-0.977	Destabilizing	0.272	N	0.619	neutral	None	None	None	None	I
K/T	0.2379	likely_benign	0.2268	benign	-0.697	Destabilizing	0.497	N	0.655	neutral	N	0.454950185	None	None	I
K/V	0.2812	likely_benign	0.2718	benign	0.06	Stabilizing	0.567	D	0.765	deleterious	None	None	None	None	I
K/W	0.8179	likely_pathogenic	0.7707	pathogenic	-0.192	Destabilizing	0.968	D	0.804	deleterious	None	None	None	None	I
K/Y	0.6769	likely_pathogenic	0.6221	pathogenic	0.093	Stabilizing	0.396	N	0.785	deleterious	None	None	None	None	I

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.