TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19307	58144;58145;58146	chr2:178594575;178594574;178594573	chr2:179459302;179459301;179459300
N2AB	17666	53221;53222;53223	chr2:178594575;178594574;178594573	chr2:179459302;179459301;179459300
N2A	16739	50440;50441;50442	chr2:178594575;178594574;178594573	chr2:179459302;179459301;179459300
N2B	10242	30949;30950;30951	chr2:178594575;178594574;178594573	chr2:179459302;179459301;179459300
Novex-1	10367	31324;31325;31326	chr2:178594575;178594574;178594573	chr2:179459302;179459301;179459300
Novex-2	10434	31525;31526;31527	chr2:178594575;178594574;178594573	chr2:179459302;179459301;179459300
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-28
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.3439
• 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
P/R	None	None	0.994	N	0.729	0.411	0.542587012665	gnomAD-4.0.0	1.20039E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31258E-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
P/A	0.1299	likely_benign	0.094	benign	-2.021	Highly Destabilizing	0.248	N	0.317	neutral	N	0.510960971	None	None	N
P/C	0.7732	likely_pathogenic	0.6536	pathogenic	-1.356	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
P/D	0.8805	likely_pathogenic	0.7746	pathogenic	-2.389	Highly Destabilizing	0.991	D	0.609	neutral	None	None	None	None	N
P/E	0.6253	likely_pathogenic	0.46	ambiguous	-2.259	Highly Destabilizing	0.97	D	0.571	neutral	None	None	None	None	N
P/F	0.8472	likely_pathogenic	0.7153	pathogenic	-1.369	Destabilizing	0.999	D	0.772	deleterious	None	None	None	None	N
P/G	0.6717	likely_pathogenic	0.5512	ambiguous	-2.461	Highly Destabilizing	0.97	D	0.618	neutral	None	None	None	None	N
P/H	0.566	likely_pathogenic	0.3923	ambiguous	-2.015	Highly Destabilizing	1.0	D	0.721	prob.delet.	N	0.510751435	None	None	N
P/I	0.5201	ambiguous	0.384	ambiguous	-0.837	Destabilizing	0.991	D	0.759	deleterious	None	None	None	None	N
P/K	0.6042	likely_pathogenic	0.4468	ambiguous	-1.819	Destabilizing	0.97	D	0.566	neutral	None	None	None	None	N
P/L	0.3323	likely_benign	0.2126	benign	-0.837	Destabilizing	0.961	D	0.684	prob.neutral	N	0.500533992	None	None	N
P/M	0.5622	ambiguous	0.4171	ambiguous	-0.652	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
P/N	0.756	likely_pathogenic	0.6207	pathogenic	-1.852	Destabilizing	0.991	D	0.701	prob.neutral	None	None	None	None	N
P/Q	0.3985	ambiguous	0.277	benign	-1.867	Destabilizing	0.996	D	0.677	prob.neutral	None	None	None	None	N
P/R	0.5235	ambiguous	0.3703	ambiguous	-1.391	Destabilizing	0.994	D	0.729	prob.delet.	N	0.478884565	None	None	N
P/S	0.325	likely_benign	0.2104	benign	-2.394	Highly Destabilizing	0.489	N	0.33	neutral	N	0.473199799	None	None	N
P/T	0.2793	likely_benign	0.1802	benign	-2.137	Highly Destabilizing	0.248	N	0.329	neutral	N	0.477403308	None	None	N
P/V	0.377	ambiguous	0.2722	benign	-1.203	Destabilizing	0.97	D	0.625	neutral	None	None	None	None	N
P/W	0.9489	likely_pathogenic	0.8837	pathogenic	-1.733	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
P/Y	0.8381	likely_pathogenic	0.6935	pathogenic	-1.403	Destabilizing	0.999	D	0.775	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.