TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14160	42703;42704;42705	chr2:178634021;178634020;178634019	chr2:179498748;179498747;179498746
N2AB	12519	37780;37781;37782	chr2:178634021;178634020;178634019	chr2:179498748;179498747;179498746
N2A	11592	34999;35000;35001	chr2:178634021;178634020;178634019	chr2:179498748;179498747;179498746
N2B	5095	15508;15509;15510	chr2:178634021;178634020;178634019	chr2:179498748;179498747;179498746
Novex-1	5220	15883;15884;15885	chr2:178634021;178634020;178634019	chr2:179498748;179498747;179498746
Novex-2	5287	16084;16085;16086	chr2:178634021;178634020;178634019	chr2:179498748;179498747;179498746
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-92
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.2929
• 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	None	None	0.001	N	0.271	0.114	0.213573922156	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	0.0766	likely_benign	0.0882	benign	-0.862	Destabilizing	0.089	N	0.389	neutral	N	0.475374113	None	None	N
T/C	0.2625	likely_benign	0.3584	ambiguous	-0.547	Destabilizing	0.94	D	0.457	neutral	None	None	None	None	N
T/D	0.3298	likely_benign	0.4104	ambiguous	-0.131	Destabilizing	0.418	N	0.509	neutral	None	None	None	None	N
T/E	0.2336	likely_benign	0.2971	benign	-0.084	Destabilizing	0.228	N	0.466	neutral	None	None	None	None	N
T/F	0.1563	likely_benign	0.1998	benign	-0.775	Destabilizing	0.264	N	0.514	neutral	None	None	None	None	N
T/G	0.2332	likely_benign	0.2988	benign	-1.166	Destabilizing	0.228	N	0.457	neutral	None	None	None	None	N
T/H	0.1251	likely_benign	0.1798	benign	-1.289	Destabilizing	0.001	N	0.37	neutral	None	None	None	None	N
T/I	0.0965	likely_benign	0.1061	benign	-0.131	Destabilizing	0.001	N	0.271	neutral	N	0.459277953	None	None	N
T/K	0.1302	likely_benign	0.1688	benign	-0.715	Destabilizing	0.129	N	0.45	neutral	None	None	None	None	N
T/L	0.0828	likely_benign	0.0939	benign	-0.131	Destabilizing	0.022	N	0.356	neutral	None	None	None	None	N
T/M	0.096	likely_benign	0.1048	benign	-0.03	Destabilizing	0.716	D	0.451	neutral	None	None	None	None	N
T/N	0.0997	likely_benign	0.1212	benign	-0.768	Destabilizing	0.351	N	0.461	neutral	N	0.462891215	None	None	N
T/P	0.3268	likely_benign	0.4156	ambiguous	-0.341	Destabilizing	0.77	D	0.487	neutral	N	0.516881199	None	None	N
T/Q	0.1533	likely_benign	0.202	benign	-0.8	Destabilizing	0.418	N	0.491	neutral	None	None	None	None	N
T/R	0.0913	likely_benign	0.125	benign	-0.553	Destabilizing	0.001	N	0.269	neutral	None	None	None	None	N
T/S	0.0931	likely_benign	0.1126	benign	-1.086	Destabilizing	0.183	N	0.437	neutral	N	0.458269349	None	None	N
T/V	0.0856	likely_benign	0.0983	benign	-0.341	Destabilizing	0.004	N	0.275	neutral	None	None	None	None	N
T/W	0.4356	ambiguous	0.5803	pathogenic	-0.749	Destabilizing	0.951	D	0.507	neutral	None	None	None	None	N
T/Y	0.1628	likely_benign	0.2377	benign	-0.502	Destabilizing	0.002	N	0.368	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.