TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23840	71743;71744;71745	chr2:178574614;178574613;178574612	chr2:179439341;179439340;179439339
N2AB	22199	66820;66821;66822	chr2:178574614;178574613;178574612	chr2:179439341;179439340;179439339
N2A	21272	64039;64040;64041	chr2:178574614;178574613;178574612	chr2:179439341;179439340;179439339
N2B	14775	44548;44549;44550	chr2:178574614;178574613;178574612	chr2:179439341;179439340;179439339
Novex-1	14900	44923;44924;44925	chr2:178574614;178574613;178574612	chr2:179439341;179439340;179439339
Novex-2	14967	45124;45125;45126	chr2:178574614;178574613;178574612	chr2:179439341;179439340;179439339
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: Fn3-61
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.5651
• 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/Q	None	None	0.999	N	0.695	0.345	0.282575091529	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
K/R	None	None	0.64	N	0.339	0.151	0.302459207581	gnomAD-4.0.0	1.59235E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86018E-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	0.6258	likely_pathogenic	0.5056	ambiguous	-0.278	Destabilizing	0.998	D	0.593	neutral	None	None	None	None	N
K/C	0.8485	likely_pathogenic	0.7884	pathogenic	-0.586	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
K/D	0.9353	likely_pathogenic	0.8948	pathogenic	-0.916	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
K/E	0.5679	likely_pathogenic	0.4272	ambiguous	-0.888	Destabilizing	0.996	D	0.539	neutral	N	0.508723168	None	None	N
K/F	0.9719	likely_pathogenic	0.9495	pathogenic	-0.609	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
K/G	0.6738	likely_pathogenic	0.5826	pathogenic	-0.536	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	N
K/H	0.5508	ambiguous	0.4983	ambiguous	-1.058	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
K/I	0.8789	likely_pathogenic	0.7797	pathogenic	0.343	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
K/L	0.8178	likely_pathogenic	0.7282	pathogenic	0.343	Stabilizing	1.0	D	0.629	neutral	None	None	None	None	N
K/M	0.6523	likely_pathogenic	0.5343	ambiguous	0.515	Stabilizing	1.0	D	0.671	neutral	N	0.515414881	None	None	N
K/N	0.8439	likely_pathogenic	0.7707	pathogenic	-0.458	Destabilizing	0.999	D	0.697	prob.neutral	N	0.468290911	None	None	N
K/P	0.9066	likely_pathogenic	0.8767	pathogenic	0.165	Stabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	N
K/Q	0.2993	likely_benign	0.2394	benign	-0.791	Destabilizing	0.999	D	0.695	prob.neutral	N	0.478192413	None	None	N
K/R	0.0783	likely_benign	0.0733	benign	-0.317	Destabilizing	0.64	D	0.339	neutral	N	0.504242855	None	None	N
K/S	0.7375	likely_pathogenic	0.6379	pathogenic	-0.91	Destabilizing	0.998	D	0.635	neutral	None	None	None	None	N
K/T	0.6427	likely_pathogenic	0.5148	ambiguous	-0.725	Destabilizing	0.999	D	0.663	neutral	N	0.475341576	None	None	N
K/V	0.7964	likely_pathogenic	0.6804	pathogenic	0.165	Stabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
K/W	0.9349	likely_pathogenic	0.8992	pathogenic	-0.577	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
K/Y	0.9129	likely_pathogenic	0.8609	pathogenic	-0.137	Destabilizing	1.0	D	0.729	prob.delet.	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.