TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17497	52714;52715;52716	chr2:178608394;178608393;178608392	chr2:179473121;179473120;179473119
N2AB	15856	47791;47792;47793	chr2:178608394;178608393;178608392	chr2:179473121;179473120;179473119
N2A	14929	45010;45011;45012	chr2:178608394;178608393;178608392	chr2:179473121;179473120;179473119
N2B	8432	25519;25520;25521	chr2:178608394;178608393;178608392	chr2:179473121;179473120;179473119
Novex-1	8557	25894;25895;25896	chr2:178608394;178608393;178608392	chr2:179473121;179473120;179473119
Novex-2	8624	26095;26096;26097	chr2:178608394;178608393;178608392	chr2:179473121;179473120;179473119
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-15
• Domain position: 28
• Structural Position: 31
• Q(SASA): 0.4328
• 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
N/D	None	None	0.999	N	0.721	0.452	0.264081493735	gnomAD-4.0.0	6.85611E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00589E-07	0	0
N/S	None	None	0.999	D	0.663	0.318	0.209622950755	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.62501E-06	0	3.66327E-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
N/A	0.503	ambiguous	0.4919	ambiguous	-0.426	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	I
N/C	0.4848	ambiguous	0.4612	ambiguous	0.434	Stabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
N/D	0.1694	likely_benign	0.1733	benign	-0.135	Destabilizing	0.999	D	0.721	prob.delet.	N	0.505069574	None	None	I
N/E	0.6857	likely_pathogenic	0.6881	pathogenic	-0.153	Destabilizing	0.999	D	0.821	deleterious	None	None	None	None	I
N/F	0.8182	likely_pathogenic	0.8245	pathogenic	-0.706	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
N/G	0.2923	likely_benign	0.2838	benign	-0.635	Destabilizing	0.999	D	0.655	neutral	None	None	None	None	I
N/H	0.2293	likely_benign	0.2303	benign	-0.707	Destabilizing	1.0	D	0.842	deleterious	N	0.474091036	None	None	I
N/I	0.7939	likely_pathogenic	0.8455	pathogenic	0.047	Stabilizing	1.0	D	0.869	deleterious	N	0.509881472	None	None	I
N/K	0.6465	likely_pathogenic	0.6769	pathogenic	0.054	Stabilizing	1.0	D	0.835	deleterious	N	0.476684702	None	None	I
N/L	0.6208	likely_pathogenic	0.6344	pathogenic	0.047	Stabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
N/M	0.717	likely_pathogenic	0.7328	pathogenic	0.575	Stabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
N/P	0.9646	likely_pathogenic	0.9787	pathogenic	-0.083	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	I
N/Q	0.6245	likely_pathogenic	0.6207	pathogenic	-0.439	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
N/R	0.6062	likely_pathogenic	0.6462	pathogenic	0.116	Stabilizing	1.0	D	0.856	deleterious	None	None	None	None	I
N/S	0.1283	likely_benign	0.1274	benign	-0.192	Destabilizing	0.999	D	0.663	neutral	D	0.523481977	None	None	I
N/T	0.4097	ambiguous	0.5263	ambiguous	-0.06	Destabilizing	0.999	D	0.824	deleterious	N	0.467240955	None	None	I
N/V	0.7482	likely_pathogenic	0.803	pathogenic	-0.083	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
N/W	0.9322	likely_pathogenic	0.9342	pathogenic	-0.638	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
N/Y	0.4003	ambiguous	0.4078	ambiguous	-0.387	Destabilizing	1.0	D	0.868	deleterious	N	0.510134962	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.