TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6017	18274;18275;18276	chr2:178730351;178730350;178730349	chr2:179595078;179595077;179595076
N2AB	5700	17323;17324;17325	chr2:178730351;178730350;178730349	chr2:179595078;179595077;179595076
N2A	4773	14542;14543;14544	chr2:178730351;178730350;178730349	chr2:179595078;179595077;179595076
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-44
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.5893
• 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	rs1307209932	None	0.008	N	0.256	0.068	0.0806252709748	gnomAD-4.0.0	3.22571E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.92894E-05	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	0.3282	likely_benign	0.3624	ambiguous	-0.35	Destabilizing	0.633	D	0.627	neutral	None	None	None	None	N
K/C	0.7863	likely_pathogenic	0.7825	pathogenic	-0.424	Destabilizing	0.996	D	0.715	prob.delet.	None	None	None	None	N
K/D	0.5658	likely_pathogenic	0.6414	pathogenic	0.398	Stabilizing	0.633	D	0.626	neutral	None	None	None	None	N
K/E	0.1779	likely_benign	0.2032	benign	0.477	Stabilizing	0.008	N	0.246	neutral	N	0.467078828	None	None	N
K/F	0.6932	likely_pathogenic	0.7296	pathogenic	-0.235	Destabilizing	0.987	D	0.695	prob.neutral	None	None	None	None	N
K/G	0.5015	ambiguous	0.5387	ambiguous	-0.649	Destabilizing	0.633	D	0.629	neutral	None	None	None	None	N
K/H	0.3707	ambiguous	0.406	ambiguous	-0.903	Destabilizing	0.923	D	0.678	prob.neutral	None	None	None	None	N
K/I	0.2832	likely_benign	0.3042	benign	0.391	Stabilizing	0.961	D	0.699	prob.neutral	None	None	None	None	N
K/L	0.2947	likely_benign	0.3181	benign	0.391	Stabilizing	0.775	D	0.637	neutral	None	None	None	None	N
K/M	0.1653	likely_benign	0.1784	benign	0.116	Stabilizing	0.995	D	0.669	neutral	N	0.482977082	None	None	N
K/N	0.37	ambiguous	0.4389	ambiguous	-0.035	Destabilizing	0.008	N	0.256	neutral	N	0.508309375	None	None	N
K/P	0.4636	ambiguous	0.4847	ambiguous	0.174	Stabilizing	0.961	D	0.675	prob.neutral	None	None	None	None	N
K/Q	0.1384	likely_benign	0.1498	benign	-0.1	Destabilizing	0.82	D	0.619	neutral	N	0.481317562	None	None	N
K/R	0.1155	likely_benign	0.115	benign	-0.245	Destabilizing	0.722	D	0.583	neutral	N	0.483664434	None	None	N
K/S	0.4091	ambiguous	0.4746	ambiguous	-0.69	Destabilizing	0.044	N	0.253	neutral	None	None	None	None	N
K/T	0.1747	likely_benign	0.1974	benign	-0.416	Destabilizing	0.565	D	0.643	neutral	N	0.511755112	None	None	N
K/V	0.3032	likely_benign	0.3278	benign	0.174	Stabilizing	0.923	D	0.621	neutral	None	None	None	None	N
K/W	0.7861	likely_pathogenic	0.8093	pathogenic	-0.149	Destabilizing	0.996	D	0.732	prob.delet.	None	None	None	None	N
K/Y	0.5589	ambiguous	0.5868	pathogenic	0.162	Stabilizing	0.987	D	0.698	prob.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.