TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5752	17479;17480;17481	chr2:178731512;178731511;178731510	chr2:179596239;179596238;179596237
N2AB	5435	16528;16529;16530	chr2:178731512;178731511;178731510	chr2:179596239;179596238;179596237
N2A	4508	13747;13748;13749	chr2:178731512;178731511;178731510	chr2:179596239;179596238;179596237
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-41
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.2291
• Predicted PPI site: N

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	rs774619432	-1.163	0.001	N	0.176	0.098	0.139678290688	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	1.78E-05	0
T/A	rs774619432	-1.163	0.001	N	0.176	0.098	0.139678290688	gnomAD-4.0.0	1.27373E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.57829E-06	7.16558E-05	0
T/I	None	None	0.002	N	0.341	0.203	0.314417295294	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25001E-06	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	0.0743	likely_benign	0.074	benign	-1.026	Destabilizing	0.001	N	0.176	neutral	N	0.443267046	None	None	N
T/C	0.3745	ambiguous	0.3424	ambiguous	-0.674	Destabilizing	0.94	D	0.498	neutral	None	None	None	None	N
T/D	0.3713	ambiguous	0.3388	benign	-0.504	Destabilizing	0.418	N	0.493	neutral	None	None	None	None	N
T/E	0.2567	likely_benign	0.2291	benign	-0.43	Destabilizing	0.418	N	0.453	neutral	None	None	None	None	N
T/F	0.1624	likely_benign	0.1532	benign	-0.799	Destabilizing	0.716	D	0.538	neutral	None	None	None	None	N
T/G	0.2447	likely_benign	0.2356	benign	-1.36	Destabilizing	0.001	N	0.347	neutral	None	None	None	None	N
T/H	0.2197	likely_benign	0.2041	benign	-1.499	Destabilizing	0.951	D	0.515	neutral	None	None	None	None	N
T/I	0.1029	likely_benign	0.0927	benign	-0.2	Destabilizing	0.002	N	0.341	neutral	N	0.482825512	None	None	N
T/K	0.2041	likely_benign	0.1813	benign	-0.748	Destabilizing	0.264	N	0.449	neutral	None	None	None	None	N
T/L	0.0792	likely_benign	0.0757	benign	-0.2	Destabilizing	0.049	N	0.429	neutral	None	None	None	None	N
T/M	0.0812	likely_benign	0.0792	benign	-0.02	Destabilizing	0.716	D	0.505	neutral	None	None	None	None	N
T/N	0.1127	likely_benign	0.108	benign	-0.892	Destabilizing	0.213	N	0.467	neutral	N	0.500640481	None	None	N
T/P	0.2303	likely_benign	0.2575	benign	-0.443	Destabilizing	0.523	D	0.537	neutral	N	0.501680631	None	None	N
T/Q	0.1953	likely_benign	0.1829	benign	-0.946	Destabilizing	0.716	D	0.527	neutral	None	None	None	None	N
T/R	0.1561	likely_benign	0.1425	benign	-0.628	Destabilizing	0.716	D	0.528	neutral	None	None	None	None	N
T/S	0.0963	likely_benign	0.0947	benign	-1.225	Destabilizing	0.007	N	0.209	neutral	N	0.481612003	None	None	N
T/V	0.09	likely_benign	0.0819	benign	-0.443	Destabilizing	0.004	N	0.194	neutral	None	None	None	None	N
T/W	0.5257	ambiguous	0.5192	ambiguous	-0.744	Destabilizing	0.983	D	0.554	neutral	None	None	None	None	N
T/Y	0.2125	likely_benign	0.2017	benign	-0.497	Destabilizing	0.836	D	0.524	neutral	None	None	None	None	N

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.