TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20161	60706;60707;60708	chr2:178591244;178591243;178591242	chr2:179455971;179455970;179455969
N2AB	18520	55783;55784;55785	chr2:178591244;178591243;178591242	chr2:179455971;179455970;179455969
N2A	17593	53002;53003;53004	chr2:178591244;178591243;178591242	chr2:179455971;179455970;179455969
N2B	11096	33511;33512;33513	chr2:178591244;178591243;178591242	chr2:179455971;179455970;179455969
Novex-1	11221	33886;33887;33888	chr2:178591244;178591243;178591242	chr2:179455971;179455970;179455969
Novex-2	11288	34087;34088;34089	chr2:178591244;178591243;178591242	chr2:179455971;179455970;179455969
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-120
• Domain position: 82
• Structural Position: 168
• Q(SASA): 0.3583
• 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/I	rs2050131574	None	1.0	N	0.879	0.436	0.72858195137	gnomAD-4.0.0	3.42189E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69892E-06	0	3.31389E-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
T/A	0.0994	likely_benign	0.115	benign	-0.436	Destabilizing	0.999	D	0.565	neutral	N	0.520170392	None	None	N
T/C	0.4888	ambiguous	0.5597	ambiguous	-0.316	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
T/D	0.4201	ambiguous	0.4976	ambiguous	0.061	Stabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
T/E	0.3247	likely_benign	0.3974	ambiguous	0.002	Stabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
T/F	0.3612	ambiguous	0.4537	ambiguous	-0.787	Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
T/G	0.3101	likely_benign	0.3679	ambiguous	-0.607	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
T/H	0.2886	likely_benign	0.3496	ambiguous	-0.927	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
T/I	0.2096	likely_benign	0.2555	benign	-0.1	Destabilizing	1.0	D	0.879	deleterious	N	0.497941823	None	None	N
T/K	0.2096	likely_benign	0.2685	benign	-0.506	Destabilizing	1.0	D	0.877	deleterious	D	0.525960213	None	None	N
T/L	0.158	likely_benign	0.1892	benign	-0.1	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
T/M	0.0928	likely_benign	0.0993	benign	0.091	Stabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
T/N	0.1352	likely_benign	0.1562	benign	-0.313	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
T/P	0.3417	ambiguous	0.4396	ambiguous	-0.181	Destabilizing	1.0	D	0.879	deleterious	N	0.514071069	None	None	N
T/Q	0.236	likely_benign	0.28	benign	-0.537	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
T/R	0.2019	likely_benign	0.2668	benign	-0.23	Destabilizing	1.0	D	0.883	deleterious	N	0.521151827	None	None	N
T/S	0.1159	likely_benign	0.1311	benign	-0.533	Destabilizing	0.999	D	0.534	neutral	N	0.43555164	None	None	N
T/V	0.1547	likely_benign	0.1782	benign	-0.181	Destabilizing	0.999	D	0.579	neutral	None	None	None	None	N
T/W	0.7134	likely_pathogenic	0.7842	pathogenic	-0.767	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
T/Y	0.3634	ambiguous	0.4424	ambiguous	-0.508	Destabilizing	1.0	D	0.902	deleterious	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.