TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17439	52540;52541;52542	chr2:178608696;178608695;178608694	chr2:179473423;179473422;179473421
N2AB	15798	47617;47618;47619	chr2:178608696;178608695;178608694	chr2:179473423;179473422;179473421
N2A	14871	44836;44837;44838	chr2:178608696;178608695;178608694	chr2:179473423;179473422;179473421
N2B	8374	25345;25346;25347	chr2:178608696;178608695;178608694	chr2:179473423;179473422;179473421
Novex-1	8499	25720;25721;25722	chr2:178608696;178608695;178608694	chr2:179473423;179473422;179473421
Novex-2	8566	25921;25922;25923	chr2:178608696;178608695;178608694	chr2:179473423;179473422;179473421
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: Fn3-14
• Domain position: 71
• Structural Position: 102
• Q(SASA): 0.3154
• 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/N	None	None	0.983	N	0.648	0.252	0.192905019026	gnomAD-4.0.0	1.23264E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.61988E-05	0	0
K/T	rs1293294438	-0.884	0.983	N	0.614	0.536	0.273503213844	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
K/T	rs1293294438	-0.884	0.983	N	0.614	0.536	0.273503213844	gnomAD-4.0.0	1.59437E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86277E-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
K/A	0.7157	likely_pathogenic	0.648	pathogenic	-0.902	Destabilizing	0.916	D	0.495	neutral	None	None	None	None	N
K/C	0.7543	likely_pathogenic	0.6959	pathogenic	-0.802	Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	N
K/D	0.8812	likely_pathogenic	0.8657	pathogenic	-0.334	Destabilizing	0.996	D	0.657	neutral	None	None	None	None	N
K/E	0.4074	ambiguous	0.3742	ambiguous	-0.172	Destabilizing	0.944	D	0.481	neutral	N	0.51063011	None	None	N
K/F	0.9393	likely_pathogenic	0.914	pathogenic	-0.435	Destabilizing	0.95	D	0.724	prob.delet.	None	None	None	None	N
K/G	0.7852	likely_pathogenic	0.7382	pathogenic	-1.319	Destabilizing	0.987	D	0.623	neutral	None	None	None	None	N
K/H	0.4417	ambiguous	0.3994	ambiguous	-1.575	Destabilizing	0.975	D	0.654	neutral	None	None	None	None	N
K/I	0.7342	likely_pathogenic	0.6708	pathogenic	0.211	Stabilizing	0.967	D	0.719	prob.delet.	N	0.475420936	None	None	N
K/L	0.715	likely_pathogenic	0.6575	pathogenic	0.211	Stabilizing	0.845	D	0.574	neutral	None	None	None	None	N
K/M	0.4634	ambiguous	0.3937	ambiguous	0.099	Stabilizing	0.999	D	0.631	neutral	None	None	None	None	N
K/N	0.6995	likely_pathogenic	0.6649	pathogenic	-0.801	Destabilizing	0.983	D	0.648	neutral	N	0.490313553	None	None	N
K/P	0.9884	likely_pathogenic	0.9824	pathogenic	-0.131	Destabilizing	0.996	D	0.641	neutral	None	None	None	None	N
K/Q	0.2249	likely_benign	0.199	benign	-0.767	Destabilizing	0.983	D	0.645	neutral	N	0.498047601	None	None	N
K/R	0.0953	likely_benign	0.0878	benign	-0.761	Destabilizing	0.944	D	0.531	neutral	N	0.498276888	None	None	N
K/S	0.7186	likely_pathogenic	0.6653	pathogenic	-1.507	Destabilizing	0.957	D	0.53	neutral	None	None	None	None	N
K/T	0.4549	ambiguous	0.3875	ambiguous	-1.111	Destabilizing	0.983	D	0.614	neutral	N	0.441012522	None	None	N
K/V	0.6498	likely_pathogenic	0.5729	pathogenic	-0.131	Destabilizing	0.975	D	0.625	neutral	None	None	None	None	N
K/W	0.8978	likely_pathogenic	0.8593	pathogenic	-0.301	Destabilizing	0.997	D	0.72	prob.delet.	None	None	None	None	N
K/Y	0.8185	likely_pathogenic	0.7763	pathogenic	-0.02	Destabilizing	0.073	N	0.322	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.