TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13886	41881;41882;41883	chr2:178635668;178635667;178635666	chr2:179500395;179500394;179500393
N2AB	12245	36958;36959;36960	chr2:178635668;178635667;178635666	chr2:179500395;179500394;179500393
N2A	11318	34177;34178;34179	chr2:178635668;178635667;178635666	chr2:179500395;179500394;179500393
N2B	4821	14686;14687;14688	chr2:178635668;178635667;178635666	chr2:179500395;179500394;179500393
Novex-1	4946	15061;15062;15063	chr2:178635668;178635667;178635666	chr2:179500395;179500394;179500393
Novex-2	5013	15262;15263;15264	chr2:178635668;178635667;178635666	chr2:179500395;179500394;179500393
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: Ig-89
• Domain position: 11
• Structural Position: 18
• Q(SASA): 0.5761
• 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/T	None	None	0.999	N	0.793	0.341	0.252162846088	gnomAD-4.0.0	6.89835E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.04439E-07	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	0.8091	likely_pathogenic	0.7795	pathogenic	0.055	Stabilizing	0.998	D	0.757	deleterious	None	None	None	None	N
K/C	0.9663	likely_pathogenic	0.9547	pathogenic	-0.377	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
K/D	0.961	likely_pathogenic	0.951	pathogenic	-0.284	Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
K/E	0.7513	likely_pathogenic	0.7094	pathogenic	-0.29	Destabilizing	0.997	D	0.697	prob.delet.	N	0.510064745	None	None	N
K/F	0.9566	likely_pathogenic	0.945	pathogenic	-0.256	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
K/G	0.8976	likely_pathogenic	0.8656	pathogenic	-0.084	Destabilizing	0.999	D	0.707	prob.delet.	None	None	None	None	N
K/H	0.7447	likely_pathogenic	0.6844	pathogenic	-0.2	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
K/I	0.7719	likely_pathogenic	0.7428	pathogenic	0.342	Stabilizing	0.999	D	0.767	deleterious	N	0.510064745	None	None	N
K/L	0.6579	likely_pathogenic	0.6211	pathogenic	0.342	Stabilizing	0.999	D	0.707	prob.delet.	None	None	None	None	N
K/M	0.6315	likely_pathogenic	0.5772	pathogenic	-0.093	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
K/N	0.8934	likely_pathogenic	0.8627	pathogenic	0.06	Stabilizing	0.999	D	0.809	deleterious	N	0.512814387	None	None	N
K/P	0.8037	likely_pathogenic	0.8026	pathogenic	0.27	Stabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
K/Q	0.4626	ambiguous	0.3906	ambiguous	-0.066	Destabilizing	0.999	D	0.821	deleterious	N	0.471263751	None	None	N
K/R	0.1561	likely_benign	0.133	benign	-0.084	Destabilizing	0.997	D	0.647	neutral	N	0.508562755	None	None	N
K/S	0.8884	likely_pathogenic	0.8644	pathogenic	-0.274	Destabilizing	0.998	D	0.741	deleterious	None	None	None	None	N
K/T	0.6971	likely_pathogenic	0.6448	pathogenic	-0.162	Destabilizing	0.999	D	0.793	deleterious	N	0.442208904	None	None	N
K/V	0.7688	likely_pathogenic	0.7349	pathogenic	0.27	Stabilizing	0.999	D	0.727	deleterious	None	None	None	None	N
K/W	0.9712	likely_pathogenic	0.9558	pathogenic	-0.375	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
K/Y	0.9271	likely_pathogenic	0.8954	pathogenic	-0.023	Destabilizing	1.0	D	0.745	deleterious	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.