TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18257	54994;54995;54996	chr2:178603918;178603917;178603916	chr2:179468645;179468644;179468643
N2AB	16616	50071;50072;50073	chr2:178603918;178603917;178603916	chr2:179468645;179468644;179468643
N2A	15689	47290;47291;47292	chr2:178603918;178603917;178603916	chr2:179468645;179468644;179468643
N2B	9192	27799;27800;27801	chr2:178603918;178603917;178603916	chr2:179468645;179468644;179468643
Novex-1	9317	28174;28175;28176	chr2:178603918;178603917;178603916	chr2:179468645;179468644;179468643
Novex-2	9384	28375;28376;28377	chr2:178603918;178603917;178603916	chr2:179468645;179468644;179468643
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-20
• Domain position: 92
• Structural Position: 120
• Q(SASA): 0.2807
• Predicted PPI site: I

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/L	rs1429008245	None	0.998	N	0.753	0.363	0.406806705197	gnomAD-4.0.0	1.59652E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.03435E-05

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	0.1004	likely_benign	0.0833	benign	-1.403	Destabilizing	0.998	D	0.63	neutral	N	0.474265166	None	None	I
P/C	0.6374	likely_pathogenic	0.6102	pathogenic	-0.789	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	I
P/D	0.9138	likely_pathogenic	0.906	pathogenic	-1.419	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	I
P/E	0.731	likely_pathogenic	0.7237	pathogenic	-1.487	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	I
P/F	0.6755	likely_pathogenic	0.5911	pathogenic	-1.3	Destabilizing	0.844	D	0.659	neutral	None	None	None	None	I
P/G	0.6879	likely_pathogenic	0.6223	pathogenic	-1.641	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	I
P/H	0.5632	ambiguous	0.5345	ambiguous	-1.175	Destabilizing	1.0	D	0.841	deleterious	N	0.508880741	None	None	I
P/I	0.5998	likely_pathogenic	0.4846	ambiguous	-0.87	Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	I
P/K	0.8425	likely_pathogenic	0.8216	pathogenic	-1.165	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
P/L	0.3828	ambiguous	0.2638	benign	-0.87	Destabilizing	0.998	D	0.753	deleterious	N	0.497129134	None	None	I
P/M	0.604	likely_pathogenic	0.5223	ambiguous	-0.544	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
P/N	0.8517	likely_pathogenic	0.8432	pathogenic	-0.83	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
P/Q	0.5464	ambiguous	0.5098	ambiguous	-1.124	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	I
P/R	0.7163	likely_pathogenic	0.6436	pathogenic	-0.512	Destabilizing	1.0	D	0.841	deleterious	N	0.507866783	None	None	I
P/S	0.3232	likely_benign	0.2887	benign	-1.226	Destabilizing	1.0	D	0.737	prob.delet.	N	0.485634698	None	None	I
P/T	0.3906	ambiguous	0.3157	benign	-1.206	Destabilizing	1.0	D	0.774	deleterious	N	0.508120272	None	None	I
P/V	0.3847	ambiguous	0.2985	benign	-1.014	Destabilizing	0.999	D	0.754	deleterious	None	None	None	None	I
P/W	0.8961	likely_pathogenic	0.8539	pathogenic	-1.402	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
P/Y	0.7179	likely_pathogenic	0.6591	pathogenic	-1.16	Destabilizing	0.998	D	0.835	deleterious	None	None	None	None	I

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.