TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24604	74035;74036;74037	chr2:178572322;178572321;178572320	chr2:179437049;179437048;179437047
N2AB	22963	69112;69113;69114	chr2:178572322;178572321;178572320	chr2:179437049;179437048;179437047
N2A	22036	66331;66332;66333	chr2:178572322;178572321;178572320	chr2:179437049;179437048;179437047
N2B	15539	46840;46841;46842	chr2:178572322;178572321;178572320	chr2:179437049;179437048;179437047
Novex-1	15664	47215;47216;47217	chr2:178572322;178572321;178572320	chr2:179437049;179437048;179437047
Novex-2	15731	47416;47417;47418	chr2:178572322;178572321;178572320	chr2:179437049;179437048;179437047
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-66
• Domain position: 86
• Structural Position: 120
• Q(SASA): 0.3124
• Predicted PPI site: I

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
P/S	None	None	0.988	N	0.697	0.427	0.340510301474	gnomAD-4.0.0	3.19777E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.75649E-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
P/A	0.2333	likely_benign	0.1444	benign	-1.423	Destabilizing	0.874	D	0.587	neutral	N	0.477734659	None	None	I
P/C	0.8476	likely_pathogenic	0.736	pathogenic	-0.833	Destabilizing	0.999	D	0.845	deleterious	None	None	None	None	I
P/D	0.9815	likely_pathogenic	0.9568	pathogenic	-1.278	Destabilizing	0.94	D	0.759	deleterious	None	None	None	None	I
P/E	0.934	likely_pathogenic	0.8714	pathogenic	-1.295	Destabilizing	0.961	D	0.743	deleterious	None	None	None	None	I
P/F	0.896	likely_pathogenic	0.783	pathogenic	-1.099	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	I
P/G	0.7274	likely_pathogenic	0.5314	ambiguous	-1.715	Destabilizing	0.994	D	0.717	prob.delet.	None	None	None	None	I
P/H	0.7894	likely_pathogenic	0.6452	pathogenic	-1.215	Destabilizing	1.0	D	0.829	deleterious	D	0.528328122	None	None	I
P/I	0.9194	likely_pathogenic	0.8368	pathogenic	-0.729	Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	I
P/K	0.9612	likely_pathogenic	0.9156	pathogenic	-1.252	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	I
P/L	0.6379	likely_pathogenic	0.4657	ambiguous	-0.729	Destabilizing	0.997	D	0.778	deleterious	D	0.522425866	None	None	I
P/M	0.8462	likely_pathogenic	0.7387	pathogenic	-0.538	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
P/N	0.9484	likely_pathogenic	0.8939	pathogenic	-0.98	Destabilizing	0.99	D	0.787	deleterious	None	None	None	None	I
P/Q	0.7939	likely_pathogenic	0.6695	pathogenic	-1.18	Destabilizing	0.998	D	0.801	deleterious	None	None	None	None	I
P/R	0.907	likely_pathogenic	0.8182	pathogenic	-0.665	Destabilizing	0.998	D	0.806	deleterious	D	0.550191359	None	None	I
P/S	0.5425	ambiguous	0.3701	ambiguous	-1.446	Destabilizing	0.988	D	0.697	prob.neutral	N	0.502688996	None	None	I
P/T	0.6533	likely_pathogenic	0.475	ambiguous	-1.364	Destabilizing	0.133	N	0.429	neutral	D	0.532340594	None	None	I
P/V	0.8043	likely_pathogenic	0.6577	pathogenic	-0.926	Destabilizing	0.986	D	0.71	prob.delet.	None	None	None	None	I
P/W	0.96	likely_pathogenic	0.8935	pathogenic	-1.269	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
P/Y	0.9136	likely_pathogenic	0.8081	pathogenic	-1.004	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	I

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.