TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1117	3574;3575;3576	chr2:178782243;178782242;178782241	chr2:179646970;179646969;179646968
N2AB	1117	3574;3575;3576	chr2:178782243;178782242;178782241	chr2:179646970;179646969;179646968
N2A	1117	3574;3575;3576	chr2:178782243;178782242;178782241	chr2:179646970;179646969;179646968
N2B	1071	3436;3437;3438	chr2:178782243;178782242;178782241	chr2:179646970;179646969;179646968
Novex-1	1071	3436;3437;3438	chr2:178782243;178782242;178782241	chr2:179646970;179646969;179646968
Novex-2	1071	3436;3437;3438	chr2:178782243;178782242;178782241	chr2:179646970;179646969;179646968
Novex-3	1117	3574;3575;3576	chr2:178782243;178782242;178782241	chr2:179646970;179646969;179646968

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-4
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.1503
• 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	1.0	N	0.789	0.572	0.368369118721	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	0.9811	likely_pathogenic	0.9832	pathogenic	-1.215	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
K/C	0.9874	likely_pathogenic	0.9872	pathogenic	-1.215	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
K/D	0.9951	likely_pathogenic	0.9961	pathogenic	-0.29	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
K/E	0.9738	likely_pathogenic	0.978	pathogenic	-0.094	Destabilizing	0.999	D	0.585	neutral	D	0.609213144	None	None	N
K/F	0.9912	likely_pathogenic	0.9922	pathogenic	-0.883	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
K/G	0.988	likely_pathogenic	0.9894	pathogenic	-1.627	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
K/H	0.8502	likely_pathogenic	0.853	pathogenic	-1.821	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
K/I	0.9534	likely_pathogenic	0.956	pathogenic	-0.1	Destabilizing	1.0	D	0.879	deleterious	N	0.46575444	None	None	N
K/L	0.9362	likely_pathogenic	0.9399	pathogenic	-0.1	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
K/M	0.9108	likely_pathogenic	0.9118	pathogenic	-0.233	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
K/N	0.9745	likely_pathogenic	0.9772	pathogenic	-0.862	Destabilizing	1.0	D	0.736	prob.delet.	N	0.471030313	None	None	N
K/P	0.9982	likely_pathogenic	0.9988	pathogenic	-0.446	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
K/Q	0.8267	likely_pathogenic	0.8379	pathogenic	-0.802	Destabilizing	1.0	D	0.723	prob.delet.	N	0.484657684	None	None	N
K/R	0.2282	likely_benign	0.2402	benign	-0.628	Destabilizing	0.999	D	0.623	neutral	N	0.421647958	None	None	N
K/S	0.9887	likely_pathogenic	0.9897	pathogenic	-1.703	Destabilizing	0.999	D	0.624	neutral	None	None	None	None	N
K/T	0.9675	likely_pathogenic	0.9703	pathogenic	-1.257	Destabilizing	1.0	D	0.789	deleterious	N	0.484880147	None	None	N
K/V	0.9395	likely_pathogenic	0.9436	pathogenic	-0.446	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
K/W	0.9922	likely_pathogenic	0.9933	pathogenic	-0.686	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
K/Y	0.956	likely_pathogenic	0.9575	pathogenic	-0.376	Destabilizing	1.0	D	0.863	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.