TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8367	25324;25325;25326	chr2:178717775;178717774;178717773	chr2:179582502;179582501;179582500
N2AB	8050	24373;24374;24375	chr2:178717775;178717774;178717773	chr2:179582502;179582501;179582500
N2A	7123	21592;21593;21594	chr2:178717775;178717774;178717773	chr2:179582502;179582501;179582500
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-69
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.5155
• 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
K/E	rs1390057796	0.253	0.469	N	0.229	0.27	0.404453528171	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
K/E	rs1390057796	0.253	0.469	N	0.229	0.27	0.404453528171	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/E	rs1390057796	0.253	0.469	N	0.229	0.27	0.404453528171	gnomAD-4.0.0	1.24343E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.69879E-06	0	0
K/R	None	None	0.976	N	0.485	0.248	0.363944505237	gnomAD-4.0.0	1.60483E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87877E-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
K/A	0.4365	ambiguous	0.5328	ambiguous	0.042	Stabilizing	0.997	D	0.567	neutral	None	None	None	None	N
K/C	0.832	likely_pathogenic	0.8694	pathogenic	-0.359	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
K/D	0.6875	likely_pathogenic	0.7653	pathogenic	-0.148	Destabilizing	0.993	D	0.57	neutral	None	None	None	None	N
K/E	0.2038	likely_benign	0.2626	benign	-0.14	Destabilizing	0.469	N	0.229	neutral	N	0.510318757	None	None	N
K/F	0.8681	likely_pathogenic	0.9081	pathogenic	-0.191	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
K/G	0.5581	ambiguous	0.659	pathogenic	-0.135	Destabilizing	0.998	D	0.547	neutral	None	None	None	None	N
K/H	0.3708	ambiguous	0.4115	ambiguous	-0.276	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	N
K/I	0.5201	ambiguous	0.601	pathogenic	0.427	Stabilizing	0.993	D	0.706	prob.neutral	N	0.496865413	None	None	N
K/L	0.5109	ambiguous	0.6015	pathogenic	0.427	Stabilizing	0.946	D	0.562	neutral	None	None	None	None	N
K/M	0.3703	ambiguous	0.4445	ambiguous	0.02	Stabilizing	1.0	D	0.634	neutral	None	None	None	None	N
K/N	0.5424	ambiguous	0.6185	pathogenic	0.071	Stabilizing	0.999	D	0.553	neutral	D	0.525096209	None	None	N
K/P	0.8228	likely_pathogenic	0.8668	pathogenic	0.325	Stabilizing	1.0	D	0.649	neutral	None	None	None	None	N
K/Q	0.1472	likely_benign	0.1712	benign	-0.057	Destabilizing	0.964	D	0.557	neutral	N	0.452945322	None	None	N
K/R	0.0793	likely_benign	0.0848	benign	-0.057	Destabilizing	0.976	D	0.485	neutral	N	0.455022835	None	None	N
K/S	0.5079	ambiguous	0.6047	pathogenic	-0.325	Destabilizing	0.997	D	0.497	neutral	None	None	None	None	N
K/T	0.2241	likely_benign	0.2858	benign	-0.18	Destabilizing	0.993	D	0.613	neutral	N	0.475630181	None	None	N
K/V	0.4631	ambiguous	0.5525	ambiguous	0.325	Stabilizing	0.988	D	0.557	neutral	None	None	None	None	N
K/W	0.8032	likely_pathogenic	0.8456	pathogenic	-0.268	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
K/Y	0.762	likely_pathogenic	0.8127	pathogenic	0.087	Stabilizing	0.997	D	0.683	prob.neutral	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.