TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28272	85039;85040;85041	chr2:178561318;178561317;178561316	chr2:179426045;179426044;179426043
N2AB	26631	80116;80117;80118	chr2:178561318;178561317;178561316	chr2:179426045;179426044;179426043
N2A	25704	77335;77336;77337	chr2:178561318;178561317;178561316	chr2:179426045;179426044;179426043
N2B	19207	57844;57845;57846	chr2:178561318;178561317;178561316	chr2:179426045;179426044;179426043
Novex-1	19332	58219;58220;58221	chr2:178561318;178561317;178561316	chr2:179426045;179426044;179426043
Novex-2	19399	58420;58421;58422	chr2:178561318;178561317;178561316	chr2:179426045;179426044;179426043
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-94
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.3759
• 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
K/Q	rs1703583612	None	0.662	N	0.36	0.19	0.17258766438	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	0	4.78927E-04
K/Q	rs1703583612	None	0.662	N	0.36	0.19	0.17258766438	gnomAD-4.0.0	4.95747E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	8.22098E-04	8.47581E-07	0	3.20215E-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
K/A	0.3138	likely_benign	0.2915	benign	-0.882	Destabilizing	0.103	N	0.31	neutral	None	None	None	None	N
K/C	0.4357	ambiguous	0.4147	ambiguous	-0.819	Destabilizing	0.965	D	0.473	neutral	None	None	None	None	N
K/D	0.7579	likely_pathogenic	0.737	pathogenic	-0.228	Destabilizing	0.561	D	0.365	neutral	None	None	None	None	N
K/E	0.2356	likely_benign	0.216	benign	-0.031	Destabilizing	0.285	N	0.298	neutral	N	0.428416945	None	None	N
K/F	0.6174	likely_pathogenic	0.5946	pathogenic	-0.292	Destabilizing	0.002	N	0.438	neutral	None	None	None	None	N
K/G	0.5065	ambiguous	0.5011	ambiguous	-1.31	Destabilizing	0.209	N	0.384	neutral	None	None	None	None	N
K/H	0.2181	likely_benign	0.2083	benign	-1.375	Destabilizing	0.965	D	0.479	neutral	None	None	None	None	N
K/I	0.2545	likely_benign	0.236	benign	0.273	Stabilizing	0.491	N	0.449	neutral	N	0.483195579	None	None	N
K/L	0.2731	likely_benign	0.2735	benign	0.273	Stabilizing	0.209	N	0.391	neutral	None	None	None	None	N
K/M	0.1599	likely_benign	0.1554	benign	-0.035	Destabilizing	0.965	D	0.478	neutral	None	None	None	None	N
K/N	0.4755	ambiguous	0.4568	ambiguous	-0.727	Destabilizing	0.491	N	0.262	neutral	N	0.508840598	None	None	N
K/P	0.9708	likely_pathogenic	0.9733	pathogenic	-0.085	Destabilizing	0.722	D	0.471	neutral	None	None	None	None	N
K/Q	0.0961	likely_benign	0.0914	benign	-0.621	Destabilizing	0.662	D	0.36	neutral	N	0.400750341	None	None	N
K/R	0.0758	likely_benign	0.0757	benign	-0.494	Destabilizing	0.491	N	0.319	neutral	N	0.471687719	None	None	N
K/S	0.3316	likely_benign	0.3036	benign	-1.436	Destabilizing	0.002	N	0.147	neutral	None	None	None	None	N
K/T	0.1422	likely_benign	0.1275	benign	-1.001	Destabilizing	0.001	N	0.252	neutral	N	0.447464065	None	None	N
K/V	0.2487	likely_benign	0.2282	benign	-0.085	Destabilizing	0.209	N	0.385	neutral	None	None	None	None	N
K/W	0.6268	likely_pathogenic	0.615	pathogenic	-0.172	Destabilizing	0.991	D	0.484	neutral	None	None	None	None	N
K/Y	0.4934	ambiguous	0.4689	ambiguous	0.122	Stabilizing	0.39	N	0.476	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.