TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23130	69613;69614;69615	chr2:178576947;178576946;178576945	chr2:179441674;179441673;179441672
N2AB	21489	64690;64691;64692	chr2:178576947;178576946;178576945	chr2:179441674;179441673;179441672
N2A	20562	61909;61910;61911	chr2:178576947;178576946;178576945	chr2:179441674;179441673;179441672
N2B	14065	42418;42419;42420	chr2:178576947;178576946;178576945	chr2:179441674;179441673;179441672
Novex-1	14190	42793;42794;42795	chr2:178576947;178576946;178576945	chr2:179441674;179441673;179441672
Novex-2	14257	42994;42995;42996	chr2:178576947;178576946;178576945	chr2:179441674;179441673;179441672
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: Fn3-55
• Domain position: 91
• Structural Position: 126
• Q(SASA): 0.5529
• 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/S	None	None	0.247	N	0.428	0.273	0.231873229951	gnomAD-4.0.0	1.59241E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86061E-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	0.066	likely_benign	0.0681	benign	-0.776	Destabilizing	0.841	D	0.67	prob.neutral	N	0.48172386	None	None	N
P/C	0.5643	likely_pathogenic	0.5479	ambiguous	-0.665	Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
P/D	0.6921	likely_pathogenic	0.6813	pathogenic	-0.586	Destabilizing	0.98	D	0.688	prob.delet.	None	None	None	None	N
P/E	0.4097	ambiguous	0.419	ambiguous	-0.664	Destabilizing	0.98	D	0.695	prob.delet.	None	None	None	None	N
P/F	0.7305	likely_pathogenic	0.7051	pathogenic	-0.759	Destabilizing	0.997	D	0.853	deleterious	None	None	None	None	N
P/G	0.4079	ambiguous	0.4059	ambiguous	-0.977	Destabilizing	0.875	D	0.74	deleterious	None	None	None	None	N
P/H	0.4156	ambiguous	0.3995	ambiguous	-0.468	Destabilizing	0.999	D	0.821	deleterious	D	0.544044473	None	None	N
P/I	0.3762	ambiguous	0.4014	ambiguous	-0.375	Destabilizing	0.99	D	0.862	deleterious	None	None	None	None	N
P/K	0.512	ambiguous	0.4987	ambiguous	-0.739	Destabilizing	0.98	D	0.672	prob.neutral	None	None	None	None	N
P/L	0.2277	likely_benign	0.2169	benign	-0.375	Destabilizing	0.974	D	0.761	deleterious	N	0.506568515	None	None	N
P/M	0.4015	ambiguous	0.3944	ambiguous	-0.386	Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
P/N	0.5173	ambiguous	0.5156	ambiguous	-0.467	Destabilizing	0.98	D	0.817	deleterious	None	None	None	None	N
P/Q	0.3137	likely_benign	0.313	benign	-0.696	Destabilizing	0.98	D	0.733	deleterious	None	None	None	None	N
P/R	0.3931	ambiguous	0.3817	ambiguous	-0.174	Destabilizing	0.974	D	0.837	deleterious	N	0.513823444	None	None	N
P/S	0.174	likely_benign	0.1736	benign	-0.867	Destabilizing	0.247	N	0.428	neutral	N	0.503276832	None	None	N
P/T	0.1347	likely_benign	0.1349	benign	-0.843	Destabilizing	0.949	D	0.748	deleterious	N	0.501542086	None	None	N
P/V	0.2352	likely_benign	0.2509	benign	-0.473	Destabilizing	0.98	D	0.768	deleterious	None	None	None	None	N
P/W	0.8407	likely_pathogenic	0.8244	pathogenic	-0.865	Destabilizing	0.999	D	0.806	deleterious	None	None	None	None	N
P/Y	0.707	likely_pathogenic	0.6886	pathogenic	-0.58	Destabilizing	0.999	D	0.848	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.