TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9625	29098;29099;29100	chr2:178707694;178707693;178707692	chr2:179572421;179572420;179572419
N2AB	9308	28147;28148;28149	chr2:178707694;178707693;178707692	chr2:179572421;179572420;179572419
N2A	8381	25366;25367;25368	chr2:178707694;178707693;178707692	chr2:179572421;179572420;179572419
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-82
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.1871
• 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/R	None	None	0.142	None	0.408	0.107	0.232513804876	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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	0.9559	likely_pathogenic	0.8722	pathogenic	-0.798	Destabilizing	0.968	D	0.569	neutral	None	None	None	None	N
K/C	0.9608	likely_pathogenic	0.914	pathogenic	-0.679	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
K/D	0.9928	likely_pathogenic	0.9798	pathogenic	0.087	Stabilizing	0.995	D	0.729	prob.delet.	None	None	None	None	N
K/E	0.9246	likely_pathogenic	0.7895	pathogenic	0.221	Stabilizing	0.958	D	0.552	neutral	None	None	None	None	N
K/F	0.9713	likely_pathogenic	0.9423	pathogenic	-0.513	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
K/G	0.9758	likely_pathogenic	0.9309	pathogenic	-1.172	Destabilizing	0.991	D	0.7	prob.neutral	None	None	None	None	N
K/H	0.6524	likely_pathogenic	0.5476	ambiguous	-1.502	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	N
K/I	0.9104	likely_pathogenic	0.7871	pathogenic	0.181	Stabilizing	0.995	D	0.807	deleterious	None	None	None	None	N
K/L	0.8284	likely_pathogenic	0.6869	pathogenic	0.181	Stabilizing	0.991	D	0.7	prob.neutral	None	None	None	None	N
K/M	0.8051	likely_pathogenic	0.6021	pathogenic	0.066	Stabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
K/N	0.9658	likely_pathogenic	0.9053	pathogenic	-0.449	Destabilizing	0.988	D	0.713	prob.delet.	None	None	None	None	N
K/P	0.995	likely_pathogenic	0.9882	pathogenic	-0.116	Destabilizing	0.998	D	0.733	prob.delet.	None	None	None	None	N
K/Q	0.5958	likely_pathogenic	0.3931	ambiguous	-0.461	Destabilizing	0.988	D	0.709	prob.delet.	None	None	None	None	N
K/R	0.1225	likely_benign	0.0968	benign	-0.564	Destabilizing	0.142	N	0.408	neutral	None	None	None	None	N
K/S	0.9734	likely_pathogenic	0.9141	pathogenic	-1.193	Destabilizing	0.968	D	0.585	neutral	None	None	None	None	N
K/T	0.9239	likely_pathogenic	0.7856	pathogenic	-0.833	Destabilizing	0.988	D	0.717	prob.delet.	None	None	None	None	N
K/V	0.891	likely_pathogenic	0.7545	pathogenic	-0.116	Destabilizing	0.995	D	0.731	prob.delet.	None	None	None	None	N
K/W	0.9589	likely_pathogenic	0.9263	pathogenic	-0.359	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
K/Y	0.9214	likely_pathogenic	0.8701	pathogenic	-0.068	Destabilizing	0.998	D	0.795	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.