TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21837	65734;65735;65736	chr2:178583673;178583672;178583671	chr2:179448400;179448399;179448398
N2AB	20196	60811;60812;60813	chr2:178583673;178583672;178583671	chr2:179448400;179448399;179448398
N2A	19269	58030;58031;58032	chr2:178583673;178583672;178583671	chr2:179448400;179448399;179448398
N2B	12772	38539;38540;38541	chr2:178583673;178583672;178583671	chr2:179448400;179448399;179448398
Novex-1	12897	38914;38915;38916	chr2:178583673;178583672;178583671	chr2:179448400;179448399;179448398
Novex-2	12964	39115;39116;39117	chr2:178583673;178583672;178583671	chr2:179448400;179448399;179448398
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Fn3-46
• Domain position: 81
• Structural Position: 111
• Q(SASA): 0.4303
• 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
R/W	rs2048289282	None	0.828	N	0.589	0.369	0.446211707333	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/W	rs2048289282	None	0.828	N	0.589	0.369	0.446211707333	gnomAD-4.0.0	6.57428E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47093E-05	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
R/A	0.7069	likely_pathogenic	0.6492	pathogenic	-1.818	Destabilizing	0.007	N	0.231	neutral	None	None	None	None	I
R/C	0.3084	likely_benign	0.2734	benign	-1.798	Destabilizing	0.864	D	0.577	neutral	None	None	None	None	I
R/D	0.9636	likely_pathogenic	0.9391	pathogenic	-0.494	Destabilizing	0.031	N	0.485	neutral	None	None	None	None	I
R/E	0.6768	likely_pathogenic	0.5687	pathogenic	-0.298	Destabilizing	0.007	N	0.207	neutral	None	None	None	None	I
R/F	0.7887	likely_pathogenic	0.7578	pathogenic	-1.298	Destabilizing	0.628	D	0.594	neutral	None	None	None	None	I
R/G	0.7114	likely_pathogenic	0.6315	pathogenic	-2.175	Highly Destabilizing	0.024	N	0.429	neutral	N	0.48479309	None	None	I
R/H	0.2493	likely_benign	0.221	benign	-2.064	Highly Destabilizing	0.356	N	0.507	neutral	None	None	None	None	I
R/I	0.426	ambiguous	0.379	ambiguous	-0.802	Destabilizing	0.136	N	0.61	neutral	None	None	None	None	I
R/K	0.0723	likely_benign	0.0655	benign	-1.347	Destabilizing	None	N	0.179	neutral	N	0.36369625	None	None	I
R/L	0.4361	ambiguous	0.406	ambiguous	-0.802	Destabilizing	0.031	N	0.429	neutral	None	None	None	None	I
R/M	0.4447	ambiguous	0.3865	ambiguous	-1.201	Destabilizing	0.56	D	0.552	neutral	N	0.449429722	None	None	I
R/N	0.8833	likely_pathogenic	0.8322	pathogenic	-1.092	Destabilizing	0.031	N	0.419	neutral	None	None	None	None	I
R/P	0.964	likely_pathogenic	0.9544	pathogenic	-1.126	Destabilizing	0.136	N	0.555	neutral	None	None	None	None	I
R/Q	0.1763	likely_benign	0.1503	benign	-1.131	Destabilizing	0.016	N	0.419	neutral	None	None	None	None	I
R/S	0.8253	likely_pathogenic	0.7617	pathogenic	-2.137	Highly Destabilizing	0.012	N	0.317	neutral	N	0.457875847	None	None	I
R/T	0.5241	ambiguous	0.4349	ambiguous	-1.72	Destabilizing	0.024	N	0.419	neutral	N	0.424840709	None	None	I
R/V	0.4546	ambiguous	0.4111	ambiguous	-1.126	Destabilizing	0.072	N	0.543	neutral	None	None	None	None	I
R/W	0.4102	ambiguous	0.3697	ambiguous	-0.731	Destabilizing	0.828	D	0.589	neutral	N	0.495740802	None	None	I
R/Y	0.6642	likely_pathogenic	0.6178	pathogenic	-0.559	Destabilizing	0.356	N	0.63	neutral	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.