TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15646	47161;47162;47163	chr2:178618614;178618613;178618612	chr2:179483341;179483340;179483339
N2AB	14005	42238;42239;42240	chr2:178618614;178618613;178618612	chr2:179483341;179483340;179483339
N2A	13078	39457;39458;39459	chr2:178618614;178618613;178618612	chr2:179483341;179483340;179483339
N2B	6581	19966;19967;19968	chr2:178618614;178618613;178618612	chr2:179483341;179483340;179483339
Novex-1	6706	20341;20342;20343	chr2:178618614;178618613;178618612	chr2:179483341;179483340;179483339
Novex-2	6773	20542;20543;20544	chr2:178618614;178618613;178618612	chr2:179483341;179483340;179483339
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-108
• Domain position: 79
• Structural Position: 166
• Q(SASA): 0.146
• 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
A/T	None	None	0.989	N	0.655	0.423	0.405422107966	gnomAD-4.0.0	8.40225E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.18751E-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
A/C	0.6389	likely_pathogenic	0.6819	pathogenic	-0.946	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
A/D	0.3427	ambiguous	0.4134	ambiguous	-1.38	Destabilizing	0.998	D	0.699	prob.neutral	None	None	None	None	N
A/E	0.3883	ambiguous	0.4468	ambiguous	-1.404	Destabilizing	0.999	D	0.706	prob.neutral	N	0.512415964	None	None	N
A/F	0.5916	likely_pathogenic	0.6358	pathogenic	-0.919	Destabilizing	0.999	D	0.728	prob.delet.	None	None	None	None	N
A/G	0.1335	likely_benign	0.1527	benign	-1.169	Destabilizing	0.054	N	0.341	neutral	N	0.503141477	None	None	N
A/H	0.6999	likely_pathogenic	0.7452	pathogenic	-1.308	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
A/I	0.428	ambiguous	0.4799	ambiguous	-0.358	Destabilizing	0.999	D	0.744	deleterious	None	None	None	None	N
A/K	0.6427	likely_pathogenic	0.6835	pathogenic	-1.444	Destabilizing	0.998	D	0.707	prob.neutral	None	None	None	None	N
A/L	0.3744	ambiguous	0.4209	ambiguous	-0.358	Destabilizing	0.992	D	0.697	prob.neutral	None	None	None	None	N
A/M	0.3685	ambiguous	0.4435	ambiguous	-0.345	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
A/N	0.427	ambiguous	0.4875	ambiguous	-1.18	Destabilizing	0.998	D	0.722	prob.delet.	None	None	None	None	N
A/P	0.9768	likely_pathogenic	0.977	pathogenic	-0.501	Destabilizing	0.999	D	0.744	deleterious	N	0.517863078	None	None	N
A/Q	0.4945	ambiguous	0.5221	ambiguous	-1.33	Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
A/R	0.6303	likely_pathogenic	0.6605	pathogenic	-1.029	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	N
A/S	0.1135	likely_benign	0.1294	benign	-1.483	Destabilizing	0.978	D	0.547	neutral	N	0.513844628	None	None	N
A/T	0.1099	likely_benign	0.1233	benign	-1.419	Destabilizing	0.989	D	0.655	neutral	N	0.515931204	None	None	N
A/V	0.196	likely_benign	0.2283	benign	-0.501	Destabilizing	0.996	D	0.637	neutral	N	0.509293798	None	None	N
A/W	0.9093	likely_pathogenic	0.9302	pathogenic	-1.286	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
A/Y	0.7066	likely_pathogenic	0.748	pathogenic	-0.897	Destabilizing	0.999	D	0.73	prob.delet.	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.