TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34290	103093;103094;103095	chr2:178533747;178533746;178533745	chr2:179398474;179398473;179398472
N2AB	32649	98170;98171;98172	chr2:178533747;178533746;178533745	chr2:179398474;179398473;179398472
N2A	31722	95389;95390;95391	chr2:178533747;178533746;178533745	chr2:179398474;179398473;179398472
N2B	25225	75898;75899;75900	chr2:178533747;178533746;178533745	chr2:179398474;179398473;179398472
Novex-1	25350	76273;76274;76275	chr2:178533747;178533746;178533745	chr2:179398474;179398473;179398472
Novex-2	25417	76474;76475;76476	chr2:178533747;178533746;178533745	chr2:179398474;179398473;179398472
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-161
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.2193
• 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/P	None	None	0.99	D	0.673	0.634	0.55350970329	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	3.66327E-05
T/R	None	None	0.942	D	0.673	0.387	0.490419987736	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
T/A	0.1297	likely_benign	0.1529	benign	-0.815	Destabilizing	0.656	D	0.542	neutral	N	0.503418644	None	None	N
T/C	0.4879	ambiguous	0.576	pathogenic	-0.413	Destabilizing	0.998	D	0.656	neutral	None	None	None	None	N
T/D	0.5353	ambiguous	0.5851	pathogenic	-0.613	Destabilizing	0.993	D	0.674	neutral	None	None	None	None	N
T/E	0.3788	ambiguous	0.4185	ambiguous	-0.467	Destabilizing	0.978	D	0.633	neutral	None	None	None	None	N
T/F	0.2501	likely_benign	0.3123	benign	-0.565	Destabilizing	0.956	D	0.711	prob.delet.	None	None	None	None	N
T/G	0.4898	ambiguous	0.5735	pathogenic	-1.193	Destabilizing	0.978	D	0.668	neutral	None	None	None	None	N
T/H	0.3124	likely_benign	0.3656	ambiguous	-1.279	Destabilizing	0.998	D	0.71	prob.delet.	None	None	None	None	N
T/I	0.1273	likely_benign	0.1428	benign	0.153	Stabilizing	0.058	N	0.357	neutral	D	0.53079003	None	None	N
T/K	0.3166	likely_benign	0.3867	ambiguous	-0.436	Destabilizing	0.942	D	0.633	neutral	N	0.514607069	None	None	N
T/L	0.1191	likely_benign	0.1413	benign	0.153	Stabilizing	0.303	N	0.518	neutral	None	None	None	None	N
T/M	0.0949	likely_benign	0.1137	benign	0.117	Stabilizing	0.559	D	0.501	neutral	None	None	None	None	N
T/N	0.2065	likely_benign	0.2558	benign	-0.868	Destabilizing	0.978	D	0.535	neutral	None	None	None	None	N
T/P	0.8335	likely_pathogenic	0.8814	pathogenic	-0.137	Destabilizing	0.99	D	0.673	neutral	D	0.544693264	None	None	N
T/Q	0.2845	likely_benign	0.3323	benign	-0.706	Destabilizing	0.978	D	0.681	prob.neutral	None	None	None	None	N
T/R	0.2563	likely_benign	0.3317	benign	-0.525	Destabilizing	0.942	D	0.673	neutral	D	0.533251545	None	None	N
T/S	0.1558	likely_benign	0.184	benign	-1.139	Destabilizing	0.822	D	0.533	neutral	N	0.51812459	None	None	N
T/V	0.1295	likely_benign	0.145	benign	-0.137	Destabilizing	0.559	D	0.484	neutral	None	None	None	None	N
T/W	0.6365	likely_pathogenic	0.6964	pathogenic	-0.702	Destabilizing	0.998	D	0.733	prob.delet.	None	None	None	None	N
T/Y	0.324	likely_benign	0.3909	ambiguous	-0.339	Destabilizing	0.978	D	0.731	prob.delet.	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.