TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31259	94000;94001;94002	chr2:178547851;178547850;178547849	chr2:179412578;179412577;179412576
N2AB	29618	89077;89078;89079	chr2:178547851;178547850;178547849	chr2:179412578;179412577;179412576
N2A	28691	86296;86297;86298	chr2:178547851;178547850;178547849	chr2:179412578;179412577;179412576
N2B	22194	66805;66806;66807	chr2:178547851;178547850;178547849	chr2:179412578;179412577;179412576
Novex-1	22319	67180;67181;67182	chr2:178547851;178547850;178547849	chr2:179412578;179412577;179412576
Novex-2	22386	67381;67382;67383	chr2:178547851;178547850;178547849	chr2:179412578;179412577;179412576
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-151
• Domain position: 42
• Structural Position: 73
• Q(SASA): 0.3789
• 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/A	None	None	0.981	N	0.455	0.288	0.202949470691	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	0.2858	likely_benign	0.3189	benign	-0.302	Destabilizing	0.981	D	0.455	neutral	N	0.514216627	None	None	N
T/C	0.8003	likely_pathogenic	0.8103	pathogenic	-0.22	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
T/D	0.4849	ambiguous	0.4783	ambiguous	0.112	Stabilizing	0.999	D	0.667	neutral	None	None	None	None	N
T/E	0.6905	likely_pathogenic	0.7021	pathogenic	0.027	Stabilizing	0.999	D	0.66	neutral	None	None	None	None	N
T/F	0.7949	likely_pathogenic	0.8094	pathogenic	-0.83	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
T/G	0.3517	ambiguous	0.3518	ambiguous	-0.416	Destabilizing	0.997	D	0.601	neutral	None	None	None	None	N
T/H	0.6176	likely_pathogenic	0.6357	pathogenic	-0.72	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
T/I	0.818	likely_pathogenic	0.8413	pathogenic	-0.124	Destabilizing	0.999	D	0.712	prob.delet.	N	0.469859576	None	None	N
T/K	0.5856	likely_pathogenic	0.6036	pathogenic	-0.349	Destabilizing	0.999	D	0.665	neutral	N	0.497439021	None	None	N
T/L	0.4424	ambiguous	0.472	ambiguous	-0.124	Destabilizing	0.998	D	0.584	neutral	None	None	None	None	N
T/M	0.2352	likely_benign	0.2516	benign	0.054	Stabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
T/N	0.1794	likely_benign	0.1804	benign	-0.094	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	N
T/P	0.6064	likely_pathogenic	0.6418	pathogenic	-0.156	Destabilizing	0.999	D	0.706	prob.neutral	N	0.469099108	None	None	N
T/Q	0.5954	likely_pathogenic	0.62	pathogenic	-0.342	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
T/R	0.5647	likely_pathogenic	0.5856	pathogenic	-0.068	Destabilizing	0.999	D	0.697	prob.neutral	N	0.514563344	None	None	N
T/S	0.1655	likely_benign	0.1649	benign	-0.291	Destabilizing	0.905	D	0.329	neutral	N	0.455818898	None	None	N
T/V	0.6782	likely_pathogenic	0.6982	pathogenic	-0.156	Destabilizing	0.998	D	0.518	neutral	None	None	None	None	N
T/W	0.8866	likely_pathogenic	0.8975	pathogenic	-0.848	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
T/Y	0.7268	likely_pathogenic	0.7408	pathogenic	-0.561	Destabilizing	1.0	D	0.777	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.