TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17332	52219;52220;52221	chr2:178609316;178609315;178609314	chr2:179474043;179474042;179474041
N2AB	15691	47296;47297;47298	chr2:178609316;178609315;178609314	chr2:179474043;179474042;179474041
N2A	14764	44515;44516;44517	chr2:178609316;178609315;178609314	chr2:179474043;179474042;179474041
N2B	8267	25024;25025;25026	chr2:178609316;178609315;178609314	chr2:179474043;179474042;179474041
Novex-1	8392	25399;25400;25401	chr2:178609316;178609315;178609314	chr2:179474043;179474042;179474041
Novex-2	8459	25600;25601;25602	chr2:178609316;178609315;178609314	chr2:179474043;179474042;179474041
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-112
• Domain position: 82
• Structural Position: 136
• Q(SASA): 0.1233
• 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/T	None	None	0.892	N	0.667	0.098	0.144782658237	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

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	0.2467	likely_benign	0.2589	benign	-0.678	Destabilizing	0.025	N	0.451	neutral	N	0.50882945	None	None	N
S/C	0.2096	likely_benign	0.2378	benign	-0.838	Destabilizing	0.995	D	0.796	deleterious	N	0.503020986	None	None	N
S/D	0.974	likely_pathogenic	0.9747	pathogenic	-2.011	Highly Destabilizing	0.957	D	0.713	prob.delet.	None	None	None	None	N
S/E	0.9851	likely_pathogenic	0.986	pathogenic	-1.792	Destabilizing	0.916	D	0.706	prob.neutral	None	None	None	None	N
S/F	0.9087	likely_pathogenic	0.9151	pathogenic	-0.639	Destabilizing	0.983	D	0.822	deleterious	N	0.454615704	None	None	N
S/G	0.4797	ambiguous	0.5002	ambiguous	-1.086	Destabilizing	0.845	D	0.695	prob.neutral	None	None	None	None	N
S/H	0.9337	likely_pathogenic	0.9402	pathogenic	-1.556	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
S/I	0.7453	likely_pathogenic	0.7596	pathogenic	0.362	Stabilizing	0.975	D	0.811	deleterious	None	None	None	None	N
S/K	0.9963	likely_pathogenic	0.9965	pathogenic	-0.32	Destabilizing	0.916	D	0.711	prob.delet.	None	None	None	None	N
S/L	0.6481	likely_pathogenic	0.6629	pathogenic	0.362	Stabilizing	0.845	D	0.776	deleterious	None	None	None	None	N
S/M	0.6821	likely_pathogenic	0.6808	pathogenic	0.283	Stabilizing	0.999	D	0.798	deleterious	None	None	None	None	N
S/N	0.7916	likely_pathogenic	0.8154	pathogenic	-1.314	Destabilizing	0.987	D	0.741	deleterious	None	None	None	None	N
S/P	0.993	likely_pathogenic	0.9923	pathogenic	0.051	Stabilizing	0.983	D	0.799	deleterious	N	0.468253415	None	None	N
S/Q	0.975	likely_pathogenic	0.9766	pathogenic	-0.994	Destabilizing	0.987	D	0.771	deleterious	None	None	None	None	N
S/R	0.9953	likely_pathogenic	0.9956	pathogenic	-0.762	Destabilizing	0.987	D	0.805	deleterious	None	None	None	None	N
S/T	0.1343	likely_benign	0.1424	benign	-0.832	Destabilizing	0.892	D	0.667	neutral	N	0.441028378	None	None	N
S/V	0.6236	likely_pathogenic	0.6447	pathogenic	0.051	Stabilizing	0.95	D	0.789	deleterious	None	None	None	None	N
S/W	0.945	likely_pathogenic	0.9447	pathogenic	-1.017	Destabilizing	0.999	D	0.808	deleterious	None	None	None	None	N
S/Y	0.8557	likely_pathogenic	0.8701	pathogenic	-0.507	Destabilizing	0.994	D	0.824	deleterious	N	0.458085197	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.