TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14196	42811;42812;42813	chr2:178633913;178633912;178633911	chr2:179498640;179498639;179498638
N2AB	12555	37888;37889;37890	chr2:178633913;178633912;178633911	chr2:179498640;179498639;179498638
N2A	11628	35107;35108;35109	chr2:178633913;178633912;178633911	chr2:179498640;179498639;179498638
N2B	5131	15616;15617;15618	chr2:178633913;178633912;178633911	chr2:179498640;179498639;179498638
Novex-1	5256	15991;15992;15993	chr2:178633913;178633912;178633911	chr2:179498640;179498639;179498638
Novex-2	5323	16192;16193;16194	chr2:178633913;178633912;178633911	chr2:179498640;179498639;179498638
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-92
• Domain position: 55
• Structural Position: 136
• Q(SASA): 0.2872
• 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
H/R	None	None	0.497	N	0.726	0.28	0.236278675362	gnomAD-4.0.0	6.84344E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99617E-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
H/A	0.6408	likely_pathogenic	0.6156	pathogenic	-1.547	Destabilizing	0.272	N	0.754	deleterious	None	None	None	None	N
H/C	0.2255	likely_benign	0.2247	benign	-1.24	Destabilizing	0.968	D	0.807	deleterious	None	None	None	None	N
H/D	0.8356	likely_pathogenic	0.826	pathogenic	-1.41	Destabilizing	0.667	D	0.757	deleterious	D	0.613135845	None	None	N
H/E	0.8298	likely_pathogenic	0.8079	pathogenic	-1.248	Destabilizing	0.431	N	0.697	prob.neutral	None	None	None	None	N
H/F	0.3211	likely_benign	0.3851	ambiguous	-0.064	Destabilizing	0.157	N	0.749	deleterious	None	None	None	None	N
H/G	0.8135	likely_pathogenic	0.7845	pathogenic	-1.939	Destabilizing	0.431	N	0.759	deleterious	None	None	None	None	N
H/I	0.6134	likely_pathogenic	0.6021	pathogenic	-0.412	Destabilizing	0.567	D	0.819	deleterious	None	None	None	None	N
H/K	0.7739	likely_pathogenic	0.7312	pathogenic	-1.203	Destabilizing	0.567	D	0.763	deleterious	None	None	None	None	N
H/L	0.3515	ambiguous	0.3211	benign	-0.412	Destabilizing	0.124	N	0.789	deleterious	N	0.502487826	None	None	N
H/M	0.7228	likely_pathogenic	0.7246	pathogenic	-0.784	Destabilizing	0.909	D	0.766	deleterious	None	None	None	None	N
H/N	0.363	ambiguous	0.3543	ambiguous	-1.623	Destabilizing	0.364	N	0.702	prob.neutral	D	0.612219266	None	None	N
H/P	0.9498	likely_pathogenic	0.9345	pathogenic	-0.776	Destabilizing	0.859	D	0.789	deleterious	D	0.612219266	None	None	N
H/Q	0.5065	ambiguous	0.468	ambiguous	-1.274	Destabilizing	0.667	D	0.73	prob.delet.	N	0.459018513	None	None	N
H/R	0.4557	ambiguous	0.372	ambiguous	-1.322	Destabilizing	0.497	N	0.726	prob.delet.	N	0.436145131	None	None	N
H/S	0.5353	ambiguous	0.5329	ambiguous	-1.84	Destabilizing	0.272	N	0.751	deleterious	None	None	None	None	N
H/T	0.6951	likely_pathogenic	0.6791	pathogenic	-1.563	Destabilizing	0.567	D	0.769	deleterious	None	None	None	None	N
H/V	0.4904	ambiguous	0.4975	ambiguous	-0.776	Destabilizing	0.567	D	0.803	deleterious	None	None	None	None	N
H/W	0.4333	ambiguous	0.4735	ambiguous	0.372	Stabilizing	0.909	D	0.765	deleterious	None	None	None	None	N
H/Y	0.0944	likely_benign	0.1047	benign	0.377	Stabilizing	None	N	0.4	neutral	N	0.473427615	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.