TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20898	62917;62918;62919	chr2:178589033;178589032;178589031	chr2:179453760;179453759;179453758
N2AB	19257	57994;57995;57996	chr2:178589033;178589032;178589031	chr2:179453760;179453759;179453758
N2A	18330	55213;55214;55215	chr2:178589033;178589032;178589031	chr2:179453760;179453759;179453758
N2B	11833	35722;35723;35724	chr2:178589033;178589032;178589031	chr2:179453760;179453759;179453758
Novex-1	11958	36097;36098;36099	chr2:178589033;178589032;178589031	chr2:179453760;179453759;179453758
Novex-2	12025	36298;36299;36300	chr2:178589033;178589032;178589031	chr2:179453760;179453759;179453758
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: Fn3-39
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.1138
• 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	rs778236151	-0.613	0.961	N	0.578	0.235	0.149567049428	gnomAD-2.1.1	4.08E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.95E-06	0
N/K	rs778236151	-0.613	0.961	N	0.578	0.235	0.149567049428	gnomAD-4.0.0	1.60076E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86038E-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	0.7813	likely_pathogenic	0.7803	pathogenic	-1.222	Destabilizing	0.871	D	0.697	prob.neutral	None	None	None	None	N
N/C	0.5551	ambiguous	0.5894	pathogenic	-0.483	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
N/D	0.7415	likely_pathogenic	0.6966	pathogenic	-1.509	Destabilizing	0.961	D	0.558	neutral	N	0.513035697	None	None	N
N/E	0.9443	likely_pathogenic	0.9375	pathogenic	-1.3	Destabilizing	0.97	D	0.571	neutral	None	None	None	None	N
N/F	0.941	likely_pathogenic	0.926	pathogenic	-0.634	Destabilizing	0.999	D	0.835	deleterious	None	None	None	None	N
N/G	0.5675	likely_pathogenic	0.5627	ambiguous	-1.625	Destabilizing	0.931	D	0.588	neutral	None	None	None	None	N
N/H	0.2848	likely_benign	0.2553	benign	-1.058	Destabilizing	0.998	D	0.615	neutral	N	0.46535918	None	None	N
N/I	0.9504	likely_pathogenic	0.948	pathogenic	-0.15	Destabilizing	0.994	D	0.828	deleterious	N	0.481270286	None	None	N
N/K	0.8893	likely_pathogenic	0.87	pathogenic	-0.424	Destabilizing	0.961	D	0.578	neutral	N	0.502490629	None	None	N
N/L	0.9072	likely_pathogenic	0.9045	pathogenic	-0.15	Destabilizing	0.985	D	0.779	deleterious	None	None	None	None	N
N/M	0.9128	likely_pathogenic	0.913	pathogenic	0.112	Stabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
N/P	0.9971	likely_pathogenic	0.9962	pathogenic	-0.48	Destabilizing	0.996	D	0.753	deleterious	None	None	None	None	N
N/Q	0.835	likely_pathogenic	0.8238	pathogenic	-1.024	Destabilizing	0.996	D	0.607	neutral	None	None	None	None	N
N/R	0.8507	likely_pathogenic	0.8295	pathogenic	-0.539	Destabilizing	0.996	D	0.61	neutral	None	None	None	None	N
N/S	0.2251	likely_benign	0.2327	benign	-1.337	Destabilizing	0.287	N	0.257	neutral	N	0.457238342	None	None	N
N/T	0.698	likely_pathogenic	0.6761	pathogenic	-0.935	Destabilizing	0.925	D	0.576	neutral	D	0.523636692	None	None	N
N/V	0.9311	likely_pathogenic	0.9294	pathogenic	-0.48	Destabilizing	0.996	D	0.783	deleterious	None	None	None	None	N
N/W	0.9724	likely_pathogenic	0.9621	pathogenic	-0.419	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
N/Y	0.4917	ambiguous	0.4373	ambiguous	-0.152	Destabilizing	0.998	D	0.771	deleterious	N	0.467178502	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.