TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18668	56227;56228;56229	chr2:178600902;178600901;178600900	chr2:179465629;179465628;179465627
N2AB	17027	51304;51305;51306	chr2:178600902;178600901;178600900	chr2:179465629;179465628;179465627
N2A	16100	48523;48524;48525	chr2:178600902;178600901;178600900	chr2:179465629;179465628;179465627
N2B	9603	29032;29033;29034	chr2:178600902;178600901;178600900	chr2:179465629;179465628;179465627
Novex-1	9728	29407;29408;29409	chr2:178600902;178600901;178600900	chr2:179465629;179465628;179465627
Novex-2	9795	29608;29609;29610	chr2:178600902;178600901;178600900	chr2:179465629;179465628;179465627
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-23
• Domain position: 90
• Structural Position: 118
• Q(SASA): 0.069
• 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
S/R	None	None	1.0	N	0.87	0.53	0.389126455913	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	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
S/A	0.6174	likely_pathogenic	0.6687	pathogenic	-0.753	Destabilizing	0.998	D	0.721	prob.delet.	None	None	None	None	N
S/C	0.8147	likely_pathogenic	0.8564	pathogenic	-0.708	Destabilizing	1.0	D	0.857	deleterious	D	0.536610236	None	None	N
S/D	0.9935	likely_pathogenic	0.9962	pathogenic	-1.496	Destabilizing	0.999	D	0.786	deleterious	None	None	None	None	N
S/E	0.9953	likely_pathogenic	0.9973	pathogenic	-1.366	Destabilizing	0.999	D	0.748	deleterious	None	None	None	None	N
S/F	0.996	likely_pathogenic	0.9978	pathogenic	-0.461	Destabilizing	1.0	D	0.914	deleterious	None	None	None	None	N
S/G	0.3181	likely_benign	0.2713	benign	-1.105	Destabilizing	0.999	D	0.741	deleterious	N	0.456304474	None	None	N
S/H	0.9931	likely_pathogenic	0.9955	pathogenic	-1.516	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
S/I	0.9941	likely_pathogenic	0.9963	pathogenic	0.119	Stabilizing	1.0	D	0.917	deleterious	D	0.536356746	None	None	N
S/K	0.9991	likely_pathogenic	0.9995	pathogenic	-0.883	Destabilizing	0.999	D	0.772	deleterious	None	None	None	None	N
S/L	0.9731	likely_pathogenic	0.9808	pathogenic	0.119	Stabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
S/M	0.9873	likely_pathogenic	0.9901	pathogenic	0.085	Stabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
S/N	0.9781	likely_pathogenic	0.9855	pathogenic	-1.299	Destabilizing	0.999	D	0.739	prob.delet.	D	0.535596278	None	None	N
S/P	0.9924	likely_pathogenic	0.9947	pathogenic	-0.137	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
S/Q	0.9938	likely_pathogenic	0.9957	pathogenic	-1.162	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
S/R	0.9976	likely_pathogenic	0.9986	pathogenic	-1.041	Destabilizing	1.0	D	0.87	deleterious	N	0.517745512	None	None	N
S/T	0.8479	likely_pathogenic	0.8608	pathogenic	-1.009	Destabilizing	0.999	D	0.732	prob.delet.	D	0.523226014	None	None	N
S/V	0.9906	likely_pathogenic	0.9936	pathogenic	-0.137	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
S/W	0.9931	likely_pathogenic	0.9965	pathogenic	-0.714	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
S/Y	0.9927	likely_pathogenic	0.9963	pathogenic	-0.342	Destabilizing	1.0	D	0.916	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.