TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16043	48352;48353;48354	chr2:178616762;178616761;178616760	chr2:179481489;179481488;179481487
N2AB	14402	43429;43430;43431	chr2:178616762;178616761;178616760	chr2:179481489;179481488;179481487
N2A	13475	40648;40649;40650	chr2:178616762;178616761;178616760	chr2:179481489;179481488;179481487
N2B	6978	21157;21158;21159	chr2:178616762;178616761;178616760	chr2:179481489;179481488;179481487
Novex-1	7103	21532;21533;21534	chr2:178616762;178616761;178616760	chr2:179481489;179481488;179481487
Novex-2	7170	21733;21734;21735	chr2:178616762;178616761;178616760	chr2:179481489;179481488;179481487
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-109
• Domain position: 76
• Structural Position: 165
• Q(SASA): 0.3093
• 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
T/A	None	None	None	N	0.133	0.072	0.0920862733494	gnomAD-4.0.0	1.59361E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.88587E-05	0	0	0	0
T/I	None	None	0.055	N	0.515	0.194	0.434716162284	gnomAD-4.0.0	4.78097E-06	None	None	None	None	I	None	0	4.57854E-05	None	0	0	None	0	0	0	0	3.02939E-05
T/R	rs2057418334	None	0.055	N	0.497	0.2	0.573444017615	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	6.57E-05	0	0	0	None	0	0	0	0	0
T/R	rs2057418334	None	0.055	N	0.497	0.2	0.573444017615	gnomAD-4.0.0	6.58406E-06	None	None	None	None	I	None	0	6.56513E-05	None	0	0	None	0	0	0	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
T/A	0.0808	likely_benign	0.0778	benign	-0.467	Destabilizing	None	N	0.133	neutral	N	0.470801149	None	None	I
T/C	0.3817	ambiguous	0.3105	benign	-0.298	Destabilizing	0.356	N	0.523	neutral	None	None	None	None	I
T/D	0.3543	ambiguous	0.3305	benign	0.046	Stabilizing	0.038	N	0.509	neutral	None	None	None	None	I
T/E	0.236	likely_benign	0.221	benign	-0.015	Destabilizing	0.038	N	0.495	neutral	None	None	None	None	I
T/F	0.3264	likely_benign	0.3043	benign	-0.8	Destabilizing	0.356	N	0.646	neutral	None	None	None	None	I
T/G	0.2221	likely_benign	0.2137	benign	-0.638	Destabilizing	0.016	N	0.623	neutral	None	None	None	None	I
T/H	0.3081	likely_benign	0.2806	benign	-0.946	Destabilizing	0.356	N	0.625	neutral	None	None	None	None	I
T/I	0.2314	likely_benign	0.2185	benign	-0.127	Destabilizing	0.055	N	0.515	neutral	N	0.499948399	None	None	I
T/K	0.2023	likely_benign	0.2001	benign	-0.544	Destabilizing	0.029	N	0.492	neutral	N	0.444519983	None	None	I
T/L	0.1501	likely_benign	0.1423	benign	-0.127	Destabilizing	0.016	N	0.493	neutral	None	None	None	None	I
T/M	0.1183	likely_benign	0.1056	benign	0.079	Stabilizing	0.356	N	0.531	neutral	None	None	None	None	I
T/N	0.1171	likely_benign	0.106	benign	-0.298	Destabilizing	0.038	N	0.373	neutral	None	None	None	None	I
T/P	0.2015	likely_benign	0.2	benign	-0.21	Destabilizing	0.055	N	0.515	neutral	N	0.511021556	None	None	I
T/Q	0.2284	likely_benign	0.2085	benign	-0.531	Destabilizing	0.214	N	0.506	neutral	None	None	None	None	I
T/R	0.1856	likely_benign	0.1758	benign	-0.257	Destabilizing	0.055	N	0.497	neutral	N	0.482959662	None	None	I
T/S	0.1014	likely_benign	0.0925	benign	-0.526	Destabilizing	None	N	0.145	neutral	N	0.346134392	None	None	I
T/V	0.1592	likely_benign	0.1512	benign	-0.21	Destabilizing	0.016	N	0.361	neutral	None	None	None	None	I
T/W	0.6636	likely_pathogenic	0.6101	pathogenic	-0.774	Destabilizing	0.864	D	0.635	neutral	None	None	None	None	I
T/Y	0.3154	likely_benign	0.2897	benign	-0.525	Destabilizing	0.356	N	0.649	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.