TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5155	15688;15689;15690	chr2:178734361;178734360;178734359	chr2:179599088;179599087;179599086
N2AB	4838	14737;14738;14739	chr2:178734361;178734360;178734359	chr2:179599088;179599087;179599086
N2A	3911	11956;11957;11958	chr2:178734361;178734360;178734359	chr2:179599088;179599087;179599086
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-34
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.7915
• 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/N	rs1215311775	0.414	0.982	N	0.686	0.335	0.218845423259	gnomAD-2.1.1	4.07E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.97E-06	0
K/N	rs1215311775	0.414	0.982	N	0.686	0.335	0.218845423259	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/N	rs1215311775	0.414	0.982	N	0.686	0.335	0.218845423259	gnomAD-4.0.0	4.35866E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.95812E-06	0	0
K/R	rs727504207	None	0.046	N	0.235	0.219	0.239901079897	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
K/A	0.4243	ambiguous	0.4495	ambiguous	-0.047	Destabilizing	0.953	D	0.647	neutral	None	None	None	None	I
K/C	0.6843	likely_pathogenic	0.727	pathogenic	-0.317	Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	I
K/D	0.6412	likely_pathogenic	0.6612	pathogenic	0.019	Stabilizing	0.993	D	0.641	neutral	None	None	None	None	I
K/E	0.2414	likely_benign	0.2542	benign	0.044	Stabilizing	0.939	D	0.611	neutral	N	0.457557886	None	None	I
K/F	0.7491	likely_pathogenic	0.7812	pathogenic	-0.127	Destabilizing	0.998	D	0.699	prob.neutral	None	None	None	None	I
K/G	0.5215	ambiguous	0.5422	ambiguous	-0.278	Destabilizing	0.976	D	0.605	neutral	None	None	None	None	I
K/H	0.2971	likely_benign	0.3199	benign	-0.493	Destabilizing	0.998	D	0.681	prob.neutral	None	None	None	None	I
K/I	0.3964	ambiguous	0.4253	ambiguous	0.491	Stabilizing	0.993	D	0.694	prob.neutral	None	None	None	None	I
K/L	0.4265	ambiguous	0.4659	ambiguous	0.491	Stabilizing	0.953	D	0.605	neutral	None	None	None	None	I
K/M	0.2817	likely_benign	0.3038	benign	0.19	Stabilizing	0.999	D	0.68	prob.neutral	N	0.518957043	None	None	I
K/N	0.4116	ambiguous	0.441	ambiguous	0.055	Stabilizing	0.982	D	0.686	prob.neutral	N	0.516951073	None	None	I
K/P	0.904	likely_pathogenic	0.9016	pathogenic	0.34	Stabilizing	0.998	D	0.698	prob.neutral	None	None	None	None	I
K/Q	0.1347	likely_benign	0.1473	benign	-0.093	Destabilizing	0.982	D	0.69	prob.neutral	N	0.488387116	None	None	I
K/R	0.082	likely_benign	0.0835	benign	-0.143	Destabilizing	0.046	N	0.235	neutral	N	0.50320625	None	None	I
K/S	0.3615	ambiguous	0.38	ambiguous	-0.441	Destabilizing	0.953	D	0.665	neutral	None	None	None	None	I
K/T	0.178	likely_benign	0.1882	benign	-0.259	Destabilizing	0.991	D	0.646	neutral	N	0.480748321	None	None	I
K/V	0.3542	ambiguous	0.3802	ambiguous	0.34	Stabilizing	0.993	D	0.615	neutral	None	None	None	None	I
K/W	0.7762	likely_pathogenic	0.7967	pathogenic	-0.121	Destabilizing	0.999	D	0.722	prob.delet.	None	None	None	None	I
K/Y	0.599	likely_pathogenic	0.6327	pathogenic	0.209	Stabilizing	0.998	D	0.691	prob.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.