TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28343	85252;85253;85254	chr2:178561105;178561104;178561103	chr2:179425832;179425831;179425830
N2AB	26702	80329;80330;80331	chr2:178561105;178561104;178561103	chr2:179425832;179425831;179425830
N2A	25775	77548;77549;77550	chr2:178561105;178561104;178561103	chr2:179425832;179425831;179425830
N2B	19278	58057;58058;58059	chr2:178561105;178561104;178561103	chr2:179425832;179425831;179425830
Novex-1	19403	58432;58433;58434	chr2:178561105;178561104;178561103	chr2:179425832;179425831;179425830
Novex-2	19470	58633;58634;58635	chr2:178561105;178561104;178561103	chr2:179425832;179425831;179425830
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-94
• Domain position: 92
• Structural Position: 124
• Q(SASA): 0.2284
• 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
T/N	None	None	0.964	D	0.697	0.476	0.514072065251	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	0
T/S	rs1703488961	None	0.657	N	0.615	0.184	0.28058544554	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
T/A	0.4187	ambiguous	0.3632	ambiguous	-1.077	Destabilizing	0.049	N	0.299	neutral	N	0.485692783	None	None	N
T/C	0.8086	likely_pathogenic	0.7815	pathogenic	-0.736	Destabilizing	0.998	D	0.728	deleterious	None	None	None	None	N
T/D	0.9755	likely_pathogenic	0.9724	pathogenic	-1.166	Destabilizing	0.973	D	0.783	deleterious	None	None	None	None	N
T/E	0.9788	likely_pathogenic	0.9758	pathogenic	-0.97	Destabilizing	0.947	D	0.761	deleterious	None	None	None	None	N
T/F	0.972	likely_pathogenic	0.9684	pathogenic	-0.726	Destabilizing	0.991	D	0.746	deleterious	None	None	None	None	N
T/G	0.8068	likely_pathogenic	0.7692	pathogenic	-1.506	Destabilizing	0.835	D	0.749	deleterious	None	None	None	None	N
T/H	0.9595	likely_pathogenic	0.9599	pathogenic	-1.595	Destabilizing	0.998	D	0.734	deleterious	None	None	None	None	N
T/I	0.8751	likely_pathogenic	0.8525	pathogenic	0.047	Stabilizing	0.964	D	0.754	deleterious	N	0.496795599	None	None	N
T/K	0.9708	likely_pathogenic	0.9703	pathogenic	-0.458	Destabilizing	0.947	D	0.779	deleterious	None	None	None	None	N
T/L	0.679	likely_pathogenic	0.6425	pathogenic	0.047	Stabilizing	0.835	D	0.75	deleterious	None	None	None	None	N
T/M	0.5675	likely_pathogenic	0.5183	ambiguous	0.021	Stabilizing	0.998	D	0.717	prob.delet.	None	None	None	None	N
T/N	0.8479	likely_pathogenic	0.8415	pathogenic	-1.112	Destabilizing	0.964	D	0.697	prob.delet.	D	0.539640381	None	None	N
T/P	0.8333	likely_pathogenic	0.8195	pathogenic	-0.295	Destabilizing	0.012	N	0.525	neutral	N	0.490936703	None	None	N
T/Q	0.9562	likely_pathogenic	0.9546	pathogenic	-0.889	Destabilizing	0.973	D	0.741	deleterious	None	None	None	None	N
T/R	0.9566	likely_pathogenic	0.9559	pathogenic	-0.66	Destabilizing	0.973	D	0.78	deleterious	None	None	None	None	N
T/S	0.2632	likely_benign	0.2478	benign	-1.386	Destabilizing	0.657	D	0.615	neutral	N	0.443706976	None	None	N
T/V	0.6468	likely_pathogenic	0.5942	pathogenic	-0.295	Destabilizing	0.835	D	0.591	neutral	None	None	None	None	N
T/W	0.9933	likely_pathogenic	0.9926	pathogenic	-0.849	Destabilizing	0.998	D	0.736	deleterious	None	None	None	None	N
T/Y	0.981	likely_pathogenic	0.9784	pathogenic	-0.472	Destabilizing	0.991	D	0.727	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.