TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24671	74236;74237;74238	chr2:178572121;178572120;178572119	chr2:179436848;179436847;179436846
N2AB	23030	69313;69314;69315	chr2:178572121;178572120;178572119	chr2:179436848;179436847;179436846
N2A	22103	66532;66533;66534	chr2:178572121;178572120;178572119	chr2:179436848;179436847;179436846
N2B	15606	47041;47042;47043	chr2:178572121;178572120;178572119	chr2:179436848;179436847;179436846
Novex-1	15731	47416;47417;47418	chr2:178572121;178572120;178572119	chr2:179436848;179436847;179436846
Novex-2	15798	47617;47618;47619	chr2:178572121;178572120;178572119	chr2:179436848;179436847;179436846
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-67
• Domain position: 56
• Structural Position: 88
• Q(SASA): 0.2958
• 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
V/A	None	None	0.25	N	0.231	0.132	0.418344901717	gnomAD-4.0.0	1.59257E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86007E-06	0	0
V/I	rs1708427922	None	0.001	N	0.131	0.112	0.391313282164	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
V/I	rs1708427922	None	0.001	N	0.131	0.112	0.391313282164	gnomAD-4.0.0	9.9187E-06	None	None	None	None	I	None	0	1.66778E-05	None	0	0	None	0	0	1.27167E-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
V/A	0.1219	likely_benign	0.1272	benign	-1.122	Destabilizing	0.25	N	0.231	neutral	N	0.430187814	None	None	I
V/C	0.6311	likely_pathogenic	0.6483	pathogenic	-0.714	Destabilizing	0.994	D	0.349	neutral	None	None	None	None	I
V/D	0.3117	likely_benign	0.2862	benign	-1.086	Destabilizing	0.799	D	0.329	neutral	N	0.470706285	None	None	I
V/E	0.3203	likely_benign	0.2948	benign	-1.055	Destabilizing	0.46	N	0.314	neutral	None	None	None	None	I
V/F	0.1814	likely_benign	0.1702	benign	-0.816	Destabilizing	0.913	D	0.391	neutral	N	0.51615336	None	None	I
V/G	0.1249	likely_benign	0.1254	benign	-1.411	Destabilizing	0.843	D	0.31	neutral	N	0.463473668	None	None	I
V/H	0.532	ambiguous	0.5121	ambiguous	-0.728	Destabilizing	0.996	D	0.365	neutral	None	None	None	None	I
V/I	0.0826	likely_benign	0.0835	benign	-0.424	Destabilizing	0.001	N	0.131	neutral	N	0.501165264	None	None	I
V/K	0.4277	ambiguous	0.4024	ambiguous	-0.9	Destabilizing	0.65	D	0.31	neutral	None	None	None	None	I
V/L	0.1771	likely_benign	0.1786	benign	-0.424	Destabilizing	0.018	N	0.273	neutral	N	0.49981847	None	None	I
V/M	0.1129	likely_benign	0.1154	benign	-0.482	Destabilizing	0.909	D	0.383	neutral	None	None	None	None	I
V/N	0.1426	likely_benign	0.1421	benign	-0.889	Destabilizing	0.492	N	0.354	neutral	None	None	None	None	I
V/P	0.7501	likely_pathogenic	0.7379	pathogenic	-0.624	Destabilizing	0.663	D	0.351	neutral	None	None	None	None	I
V/Q	0.3284	likely_benign	0.3162	benign	-1.0	Destabilizing	0.904	D	0.375	neutral	None	None	None	None	I
V/R	0.4681	ambiguous	0.4325	ambiguous	-0.408	Destabilizing	0.966	D	0.391	neutral	None	None	None	None	I
V/S	0.1165	likely_benign	0.1201	benign	-1.329	Destabilizing	0.034	N	0.196	neutral	None	None	None	None	I
V/T	0.1034	likely_benign	0.1079	benign	-1.186	Destabilizing	0.005	N	0.081	neutral	None	None	None	None	I
V/W	0.8502	likely_pathogenic	0.836	pathogenic	-1.022	Destabilizing	0.999	D	0.425	neutral	None	None	None	None	I
V/Y	0.5238	ambiguous	0.5025	ambiguous	-0.685	Destabilizing	0.966	D	0.393	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.