TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30266	91021;91022;91023	chr2:178552104;178552103;178552102	chr2:179416831;179416830;179416829
N2AB	28625	86098;86099;86100	chr2:178552104;178552103;178552102	chr2:179416831;179416830;179416829
N2A	27698	83317;83318;83319	chr2:178552104;178552103;178552102	chr2:179416831;179416830;179416829
N2B	21201	63826;63827;63828	chr2:178552104;178552103;178552102	chr2:179416831;179416830;179416829
Novex-1	21326	64201;64202;64203	chr2:178552104;178552103;178552102	chr2:179416831;179416830;179416829
Novex-2	21393	64402;64403;64404	chr2:178552104;178552103;178552102	chr2:179416831;179416830;179416829
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-108
• Domain position: 43
• Structural Position: 44
• Q(SASA): 0.2173
• 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/G	None	None	1.0	N	0.693	0.522	0.483521307902	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
E/A	0.5836	likely_pathogenic	0.3996	ambiguous	-0.931	Destabilizing	0.999	D	0.657	neutral	N	0.477840472	None	None	N
E/C	0.9694	likely_pathogenic	0.9525	pathogenic	-0.547	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/D	0.2115	likely_benign	0.1522	benign	-1.237	Destabilizing	0.999	D	0.489	neutral	N	0.401657205	None	None	N
E/F	0.9775	likely_pathogenic	0.9602	pathogenic	-0.359	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/G	0.6521	likely_pathogenic	0.4756	ambiguous	-1.311	Destabilizing	1.0	D	0.693	prob.neutral	N	0.480171104	None	None	N
E/H	0.9037	likely_pathogenic	0.8345	pathogenic	-0.669	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
E/I	0.8348	likely_pathogenic	0.735	pathogenic	0.112	Stabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
E/K	0.6999	likely_pathogenic	0.5191	ambiguous	-0.765	Destabilizing	0.999	D	0.603	neutral	N	0.514555849	None	None	N
E/L	0.8224	likely_pathogenic	0.7085	pathogenic	0.112	Stabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/M	0.845	likely_pathogenic	0.7522	pathogenic	0.599	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
E/N	0.6638	likely_pathogenic	0.4909	ambiguous	-1.238	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
E/P	0.9062	likely_pathogenic	0.8091	pathogenic	-0.214	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/Q	0.4711	ambiguous	0.3327	benign	-1.093	Destabilizing	1.0	D	0.644	neutral	D	0.522905974	None	None	N
E/R	0.8424	likely_pathogenic	0.7104	pathogenic	-0.478	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
E/S	0.6957	likely_pathogenic	0.5159	ambiguous	-1.576	Destabilizing	0.999	D	0.658	neutral	None	None	None	None	N
E/T	0.7876	likely_pathogenic	0.6285	pathogenic	-1.258	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
E/V	0.6748	likely_pathogenic	0.528	ambiguous	-0.214	Destabilizing	1.0	D	0.783	deleterious	N	0.488071142	None	None	N
E/W	0.9914	likely_pathogenic	0.985	pathogenic	-0.11	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
E/Y	0.9562	likely_pathogenic	0.921	pathogenic	-0.11	Destabilizing	1.0	D	0.785	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.