TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13713	41362;41363;41364	chr2:178636590;178636589;178636588	chr2:179501317;179501316;179501315
N2AB	12072	36439;36440;36441	chr2:178636590;178636589;178636588	chr2:179501317;179501316;179501315
N2A	11145	33658;33659;33660	chr2:178636590;178636589;178636588	chr2:179501317;179501316;179501315
N2B	4648	14167;14168;14169	chr2:178636590;178636589;178636588	chr2:179501317;179501316;179501315
Novex-1	4773	14542;14543;14544	chr2:178636590;178636589;178636588	chr2:179501317;179501316;179501315
Novex-2	4840	14743;14744;14745	chr2:178636590;178636589;178636588	chr2:179501317;179501316;179501315
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-87
• Domain position: 30
• Structural Position: 41
• Q(SASA): 0.4161
• 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
S/C	None	None	1.0	D	0.711	0.544	0.683316155328	gnomAD-4.0.0	1.36869E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79922E-06	0	0
S/P	None	None	1.0	N	0.715	0.547	0.394685799254	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
S/A	0.3243	likely_benign	0.3523	ambiguous	-0.522	Destabilizing	0.997	D	0.525	neutral	N	0.506009482	None	None	N
S/C	0.904	likely_pathogenic	0.9164	pathogenic	-0.349	Destabilizing	1.0	D	0.711	prob.delet.	D	0.620174643	None	None	N
S/D	0.9738	likely_pathogenic	0.9772	pathogenic	0.084	Stabilizing	0.999	D	0.678	prob.neutral	None	None	None	None	N
S/E	0.9758	likely_pathogenic	0.9779	pathogenic	-0.01	Destabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	N
S/F	0.9598	likely_pathogenic	0.9731	pathogenic	-1.082	Destabilizing	1.0	D	0.781	deleterious	N	0.502656465	None	None	N
S/G	0.5424	ambiguous	0.6109	pathogenic	-0.635	Destabilizing	0.999	D	0.579	neutral	None	None	None	None	N
S/H	0.9637	likely_pathogenic	0.9709	pathogenic	-1.16	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
S/I	0.9175	likely_pathogenic	0.9399	pathogenic	-0.35	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
S/K	0.9954	likely_pathogenic	0.9959	pathogenic	-0.55	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
S/L	0.7864	likely_pathogenic	0.8366	pathogenic	-0.35	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
S/M	0.8849	likely_pathogenic	0.9179	pathogenic	0.002	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
S/N	0.8571	likely_pathogenic	0.8814	pathogenic	-0.271	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
S/P	0.765	likely_pathogenic	0.7819	pathogenic	-0.379	Destabilizing	1.0	D	0.715	prob.delet.	N	0.473771128	None	None	N
S/Q	0.9628	likely_pathogenic	0.9685	pathogenic	-0.564	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
S/R	0.993	likely_pathogenic	0.9938	pathogenic	-0.331	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
S/T	0.5159	ambiguous	0.5627	ambiguous	-0.407	Destabilizing	0.999	D	0.582	neutral	N	0.498963236	None	None	N
S/V	0.8731	likely_pathogenic	0.9045	pathogenic	-0.379	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
S/W	0.9716	likely_pathogenic	0.98	pathogenic	-1.039	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
S/Y	0.9431	likely_pathogenic	0.9596	pathogenic	-0.783	Destabilizing	1.0	D	0.779	deleterious	N	0.511141902	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.