TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27055	81388;81389;81390	chr2:178564969;178564968;178564967	chr2:179429696;179429695;179429694
N2AB	25414	76465;76466;76467	chr2:178564969;178564968;178564967	chr2:179429696;179429695;179429694
N2A	24487	73684;73685;73686	chr2:178564969;178564968;178564967	chr2:179429696;179429695;179429694
N2B	17990	54193;54194;54195	chr2:178564969;178564968;178564967	chr2:179429696;179429695;179429694
Novex-1	18115	54568;54569;54570	chr2:178564969;178564968;178564967	chr2:179429696;179429695;179429694
Novex-2	18182	54769;54770;54771	chr2:178564969;178564968;178564967	chr2:179429696;179429695;179429694
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: Fn3-84
• Domain position: 84
• Structural Position: 117
• Q(SASA): 0.4138
• Predicted PPI site: I

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/E	None	None	0.324	N	0.503	0.239	0.166414681773	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
K/N	None	None	0.627	N	0.584	0.109	0.159798565429	gnomAD-4.0.0	1.59565E-06	None	None	None	None	I	None	0	0	None	0	2.77469E-05	None	0	0	0	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	0.6367	likely_pathogenic	0.6031	pathogenic	-0.55	Destabilizing	0.116	N	0.489	neutral	None	None	None	None	I
K/C	0.7492	likely_pathogenic	0.7105	pathogenic	-0.652	Destabilizing	0.981	D	0.652	neutral	None	None	None	None	I
K/D	0.9097	likely_pathogenic	0.9082	pathogenic	0.243	Stabilizing	0.69	D	0.59	neutral	None	None	None	None	I
K/E	0.4116	ambiguous	0.4218	ambiguous	0.344	Stabilizing	0.324	N	0.503	neutral	N	0.480960564	None	None	I
K/F	0.8871	likely_pathogenic	0.8739	pathogenic	-0.377	Destabilizing	0.69	D	0.662	neutral	None	None	None	None	I
K/G	0.7903	likely_pathogenic	0.7734	pathogenic	-0.861	Destabilizing	0.002	N	0.439	neutral	None	None	None	None	I
K/H	0.5132	ambiguous	0.4717	ambiguous	-0.955	Destabilizing	0.981	D	0.585	neutral	None	None	None	None	I
K/I	0.3978	ambiguous	0.398	ambiguous	0.235	Stabilizing	0.193	N	0.645	neutral	N	0.453950108	None	None	I
K/L	0.5122	ambiguous	0.4945	ambiguous	0.235	Stabilizing	0.043	N	0.561	neutral	None	None	None	None	I
K/M	0.3512	ambiguous	0.338	benign	-0.046	Destabilizing	0.043	N	0.474	neutral	None	None	None	None	I
K/N	0.7293	likely_pathogenic	0.7265	pathogenic	-0.258	Destabilizing	0.627	D	0.584	neutral	N	0.469785395	None	None	I
K/P	0.8488	likely_pathogenic	0.8428	pathogenic	0.002	Stabilizing	0.818	D	0.617	neutral	None	None	None	None	I
K/Q	0.2096	likely_benign	0.19	benign	-0.294	Destabilizing	0.627	D	0.613	neutral	N	0.467610051	None	None	I
K/R	0.0933	likely_benign	0.0901	benign	-0.275	Destabilizing	0.324	N	0.568	neutral	N	0.452237954	None	None	I
K/S	0.723	likely_pathogenic	0.7008	pathogenic	-0.955	Destabilizing	0.241	N	0.461	neutral	None	None	None	None	I
K/T	0.3504	ambiguous	0.3361	benign	-0.647	Destabilizing	0.006	N	0.357	neutral	N	0.456566338	None	None	I
K/V	0.397	ambiguous	0.3779	ambiguous	0.002	Stabilizing	0.002	N	0.461	neutral	None	None	None	None	I
K/W	0.8927	likely_pathogenic	0.8826	pathogenic	-0.26	Destabilizing	0.981	D	0.673	neutral	None	None	None	None	I
K/Y	0.7862	likely_pathogenic	0.7697	pathogenic	0.027	Stabilizing	0.818	D	0.658	neutral	None	None	None	None	I

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.