TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33212	99859;99860;99861	chr2:178537573;178537572;178537571	chr2:179402300;179402299;179402298
N2AB	31571	94936;94937;94938	chr2:178537573;178537572;178537571	chr2:179402300;179402299;179402298
N2A	30644	92155;92156;92157	chr2:178537573;178537572;178537571	chr2:179402300;179402299;179402298
N2B	24147	72664;72665;72666	chr2:178537573;178537572;178537571	chr2:179402300;179402299;179402298
Novex-1	24272	73039;73040;73041	chr2:178537573;178537572;178537571	chr2:179402300;179402299;179402298
Novex-2	24339	73240;73241;73242	chr2:178537573;178537572;178537571	chr2:179402300;179402299;179402298
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-157
• Domain position: 10
• Structural Position: 25
• Q(SASA): 0.2729
• 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
S/C	None	None	0.997	N	0.365	0.333	0.354396617058	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
S/P	rs1692192706	None	0.969	N	0.369	0.291	0.218845423259	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
S/P	rs1692192706	None	0.969	N	0.369	0.291	0.218845423259	gnomAD-4.0.0	6.57065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46998E-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
S/A	0.1312	likely_benign	0.1354	benign	-0.656	Destabilizing	0.028	N	0.367	neutral	N	0.45590183	None	None	N
S/C	0.1866	likely_benign	0.2042	benign	-0.418	Destabilizing	0.997	D	0.365	neutral	N	0.500308755	None	None	N
S/D	0.5102	ambiguous	0.5212	ambiguous	-0.143	Destabilizing	0.852	D	0.347	neutral	None	None	None	None	N
S/E	0.6398	likely_pathogenic	0.6141	pathogenic	-0.215	Destabilizing	0.889	D	0.346	neutral	None	None	None	None	N
S/F	0.478	ambiguous	0.5144	ambiguous	-1.16	Destabilizing	0.991	D	0.458	neutral	N	0.500308755	None	None	N
S/G	0.0902	likely_benign	0.1122	benign	-0.805	Destabilizing	0.014	N	0.185	neutral	None	None	None	None	N
S/H	0.5097	ambiguous	0.4991	ambiguous	-1.346	Destabilizing	0.999	D	0.363	neutral	None	None	None	None	N
S/I	0.4479	ambiguous	0.5093	ambiguous	-0.384	Destabilizing	0.987	D	0.461	neutral	None	None	None	None	N
S/K	0.7854	likely_pathogenic	0.7689	pathogenic	-0.606	Destabilizing	0.955	D	0.345	neutral	None	None	None	None	N
S/L	0.2458	likely_benign	0.2849	benign	-0.384	Destabilizing	0.915	D	0.431	neutral	None	None	None	None	N
S/M	0.3191	likely_benign	0.3517	ambiguous	0.051	Stabilizing	0.999	D	0.361	neutral	None	None	None	None	N
S/N	0.1608	likely_benign	0.1674	benign	-0.412	Destabilizing	0.402	N	0.401	neutral	None	None	None	None	N
S/P	0.9426	likely_pathogenic	0.9633	pathogenic	-0.446	Destabilizing	0.969	D	0.369	neutral	N	0.499962038	None	None	N
S/Q	0.5885	likely_pathogenic	0.5767	pathogenic	-0.714	Destabilizing	0.993	D	0.384	neutral	None	None	None	None	N
S/R	0.7336	likely_pathogenic	0.7257	pathogenic	-0.375	Destabilizing	0.993	D	0.371	neutral	None	None	None	None	N
S/T	0.1114	likely_benign	0.1262	benign	-0.518	Destabilizing	0.001	N	0.158	neutral	N	0.402395419	None	None	N
S/V	0.3997	ambiguous	0.4424	ambiguous	-0.446	Destabilizing	0.801	D	0.421	neutral	None	None	None	None	N
S/W	0.6606	likely_pathogenic	0.6922	pathogenic	-1.094	Destabilizing	0.999	D	0.523	neutral	None	None	None	None	N
S/Y	0.3953	ambiguous	0.4037	ambiguous	-0.84	Destabilizing	0.997	D	0.455	neutral	N	0.481280277	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.