TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14722	44389;44390;44391	chr2:178630358;178630357;178630356	chr2:179495085;179495084;179495083
N2AB	13081	39466;39467;39468	chr2:178630358;178630357;178630356	chr2:179495085;179495084;179495083
N2A	12154	36685;36686;36687	chr2:178630358;178630357;178630356	chr2:179495085;179495084;179495083
N2B	5657	17194;17195;17196	chr2:178630358;178630357;178630356	chr2:179495085;179495084;179495083
Novex-1	5782	17569;17570;17571	chr2:178630358;178630357;178630356	chr2:179495085;179495084;179495083
Novex-2	5849	17770;17771;17772	chr2:178630358;178630357;178630356	chr2:179495085;179495084;179495083
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-98
• Domain position: 48
• Structural Position: 123
• Q(SASA): 0.2677
• 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
I/V	None	None	0.647	N	0.396	0.158	0.256283259241	gnomAD-4.0.0	1.60139E-06	None	None	None	None	N	None	0	0	None	0	2.79142E-05	None	0	0	0	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
I/A	0.8768	likely_pathogenic	0.901	pathogenic	-2.301	Highly Destabilizing	0.964	D	0.637	neutral	None	None	None	None	N
I/C	0.9429	likely_pathogenic	0.9596	pathogenic	-1.362	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
I/D	0.9787	likely_pathogenic	0.9845	pathogenic	-2.346	Highly Destabilizing	0.998	D	0.876	deleterious	None	None	None	None	N
I/E	0.901	likely_pathogenic	0.9236	pathogenic	-2.242	Highly Destabilizing	0.998	D	0.874	deleterious	None	None	None	None	N
I/F	0.3184	likely_benign	0.3469	ambiguous	-1.531	Destabilizing	0.986	D	0.651	prob.neutral	D	0.592588341	None	None	N
I/G	0.9546	likely_pathogenic	0.9647	pathogenic	-2.741	Highly Destabilizing	0.998	D	0.869	deleterious	None	None	None	None	N
I/H	0.9088	likely_pathogenic	0.934	pathogenic	-2.138	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
I/K	0.7451	likely_pathogenic	0.8143	pathogenic	-1.72	Destabilizing	0.995	D	0.873	deleterious	None	None	None	None	N
I/L	0.2317	likely_benign	0.282	benign	-1.083	Destabilizing	0.026	N	0.157	neutral	N	0.457350714	None	None	N
I/M	0.1208	likely_benign	0.1333	benign	-0.779	Destabilizing	0.986	D	0.621	neutral	N	0.437386531	None	None	N
I/N	0.7665	likely_pathogenic	0.8212	pathogenic	-1.694	Destabilizing	0.998	D	0.877	deleterious	D	0.596488286	None	None	N
I/P	0.975	likely_pathogenic	0.9821	pathogenic	-1.464	Destabilizing	0.998	D	0.877	deleterious	None	None	None	None	N
I/Q	0.7994	likely_pathogenic	0.8562	pathogenic	-1.757	Destabilizing	0.998	D	0.849	deleterious	None	None	None	None	N
I/R	0.682	likely_pathogenic	0.7584	pathogenic	-1.21	Destabilizing	0.998	D	0.873	deleterious	None	None	None	None	N
I/S	0.8433	likely_pathogenic	0.8762	pathogenic	-2.314	Highly Destabilizing	0.998	D	0.786	deleterious	D	0.594343789	None	None	N
I/T	0.7938	likely_pathogenic	0.814	pathogenic	-2.088	Highly Destabilizing	0.993	D	0.768	deleterious	D	0.530444266	None	None	N
I/V	0.2027	likely_benign	0.2208	benign	-1.464	Destabilizing	0.647	D	0.396	neutral	N	0.461163373	None	None	N
I/W	0.8714	likely_pathogenic	0.8955	pathogenic	-1.82	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
I/Y	0.7446	likely_pathogenic	0.8031	pathogenic	-1.571	Destabilizing	0.998	D	0.739	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.