TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14887	44884;44885;44886	chr2:178624621;178624620;178624619	chr2:179489348;179489347;179489346
N2AB	13246	39961;39962;39963	chr2:178624621;178624620;178624619	chr2:179489348;179489347;179489346
N2A	12319	37180;37181;37182	chr2:178624621;178624620;178624619	chr2:179489348;179489347;179489346
N2B	5822	17689;17690;17691	chr2:178624621;178624620;178624619	chr2:179489348;179489347;179489346
Novex-1	5947	18064;18065;18066	chr2:178624621;178624620;178624619	chr2:179489348;179489347;179489346
Novex-2	6014	18265;18266;18267	chr2:178624621;178624620;178624619	chr2:179489348;179489347;179489346
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-100
• Domain position: 35
• Structural Position: 50
• Q(SASA): 0.1524
• 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	0.121	N	0.263	0.128	0.151104730317	gnomAD-4.0.0	1.59364E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86256E-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	0.8416	likely_pathogenic	0.7838	pathogenic	-1.332	Destabilizing	0.983	D	0.548	neutral	None	None	None	None	N
K/C	0.8468	likely_pathogenic	0.7928	pathogenic	-1.395	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
K/D	0.972	likely_pathogenic	0.9646	pathogenic	-1.118	Destabilizing	0.998	D	0.736	prob.delet.	None	None	None	None	N
K/E	0.681	likely_pathogenic	0.5627	ambiguous	-0.868	Destabilizing	0.978	D	0.487	neutral	D	0.5577411	None	None	N
K/F	0.9434	likely_pathogenic	0.9138	pathogenic	-0.795	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
K/G	0.9245	likely_pathogenic	0.882	pathogenic	-1.809	Destabilizing	0.998	D	0.713	prob.delet.	None	None	None	None	N
K/H	0.5578	ambiguous	0.4974	ambiguous	-1.985	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
K/I	0.742	likely_pathogenic	0.6435	pathogenic	-0.012	Destabilizing	0.999	D	0.832	deleterious	N	0.500158519	None	None	N
K/L	0.7385	likely_pathogenic	0.6393	pathogenic	-0.012	Destabilizing	0.995	D	0.713	prob.delet.	None	None	None	None	N
K/M	0.609	likely_pathogenic	0.5143	ambiguous	-0.181	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
K/N	0.916	likely_pathogenic	0.8863	pathogenic	-1.406	Destabilizing	0.997	D	0.651	neutral	N	0.464954385	None	None	N
K/P	0.9924	likely_pathogenic	0.9889	pathogenic	-0.427	Destabilizing	0.999	D	0.748	deleterious	None	None	None	None	N
K/Q	0.3045	likely_benign	0.2297	benign	-1.202	Destabilizing	0.994	D	0.635	neutral	N	0.464726133	None	None	N
K/R	0.0957	likely_benign	0.0801	benign	-0.947	Destabilizing	0.121	N	0.263	neutral	N	0.35870073	None	None	N
K/S	0.8876	likely_pathogenic	0.8453	pathogenic	-2.112	Highly Destabilizing	0.992	D	0.539	neutral	None	None	None	None	N
K/T	0.7568	likely_pathogenic	0.6927	pathogenic	-1.591	Destabilizing	0.997	D	0.711	prob.delet.	N	0.50120242	None	None	N
K/V	0.7325	likely_pathogenic	0.6454	pathogenic	-0.427	Destabilizing	0.998	D	0.763	deleterious	None	None	None	None	N
K/W	0.9087	likely_pathogenic	0.844	pathogenic	-0.702	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
K/Y	0.8546	likely_pathogenic	0.8034	pathogenic	-0.377	Destabilizing	0.999	D	0.808	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.