TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18472	55639;55640;55641	chr2:178601676;178601675;178601674	chr2:179466403;179466402;179466401
N2AB	16831	50716;50717;50718	chr2:178601676;178601675;178601674	chr2:179466403;179466402;179466401
N2A	15904	47935;47936;47937	chr2:178601676;178601675;178601674	chr2:179466403;179466402;179466401
N2B	9407	28444;28445;28446	chr2:178601676;178601675;178601674	chr2:179466403;179466402;179466401
Novex-1	9532	28819;28820;28821	chr2:178601676;178601675;178601674	chr2:179466403;179466402;179466401
Novex-2	9599	29020;29021;29022	chr2:178601676;178601675;178601674	chr2:179466403;179466402;179466401
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-115
• Domain position: 91
• Structural Position: 172
• Q(SASA): 0.0616
• 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
C/G	rs2053489886	None	0.784	N	0.671	0.345	0.748464722647	gnomAD-4.0.0	4.83489E-06	None	None	None	None	N	None	6.16789E-05	0	None	0	0	None	0	0	0	0	8.37633E-05
C/R	rs2053489886	None	0.975	N	0.769	0.366	0.793074248023	gnomAD-4.0.0	6.90698E-07	None	None	None	None	N	None	3.08394E-05	0	None	0	0	None	0	0	0	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
C/A	0.645	likely_pathogenic	0.5885	pathogenic	-2.055	Highly Destabilizing	0.085	N	0.347	neutral	None	None	None	None	N
C/D	0.9961	likely_pathogenic	0.9962	pathogenic	-1.047	Destabilizing	0.936	D	0.748	deleterious	None	None	None	None	N
C/E	0.9961	likely_pathogenic	0.9961	pathogenic	-0.847	Destabilizing	0.828	D	0.714	prob.delet.	None	None	None	None	N
C/F	0.5211	ambiguous	0.4628	ambiguous	-1.317	Destabilizing	0.642	D	0.714	prob.delet.	N	0.477838193	None	None	N
C/G	0.6478	likely_pathogenic	0.6359	pathogenic	-2.435	Highly Destabilizing	0.784	D	0.671	neutral	N	0.503659357	None	None	N
C/H	0.9776	likely_pathogenic	0.975	pathogenic	-2.464	Highly Destabilizing	0.981	D	0.726	prob.delet.	None	None	None	None	N
C/I	0.4088	ambiguous	0.3652	ambiguous	-1.032	Destabilizing	0.001	N	0.363	neutral	None	None	None	None	N
C/K	0.9956	likely_pathogenic	0.9956	pathogenic	-1.241	Destabilizing	0.828	D	0.699	prob.neutral	None	None	None	None	N
C/L	0.5528	ambiguous	0.4994	ambiguous	-1.032	Destabilizing	0.085	N	0.492	neutral	None	None	None	None	N
C/M	0.7606	likely_pathogenic	0.7078	pathogenic	0.146	Stabilizing	0.893	D	0.747	deleterious	None	None	None	None	N
C/N	0.9752	likely_pathogenic	0.9739	pathogenic	-1.644	Destabilizing	0.981	D	0.767	deleterious	None	None	None	None	N
C/P	0.994	likely_pathogenic	0.9956	pathogenic	-1.349	Destabilizing	0.936	D	0.761	deleterious	None	None	None	None	N
C/Q	0.9857	likely_pathogenic	0.9846	pathogenic	-1.302	Destabilizing	0.981	D	0.762	deleterious	None	None	None	None	N
C/R	0.9695	likely_pathogenic	0.9702	pathogenic	-1.411	Destabilizing	0.975	D	0.769	deleterious	N	0.485123352	None	None	N
C/S	0.7735	likely_pathogenic	0.7413	pathogenic	-2.13	Highly Destabilizing	0.6	D	0.597	neutral	N	0.521551684	None	None	N
C/T	0.7493	likely_pathogenic	0.7055	pathogenic	-1.717	Destabilizing	0.495	N	0.589	neutral	None	None	None	None	N
C/V	0.2868	likely_benign	0.2609	benign	-1.349	Destabilizing	0.001	N	0.321	neutral	None	None	None	None	N
C/W	0.9337	likely_pathogenic	0.9293	pathogenic	-1.447	Destabilizing	0.993	D	0.703	prob.neutral	N	0.485376842	None	None	N
C/Y	0.8336	likely_pathogenic	0.8143	pathogenic	-1.397	Destabilizing	0.917	D	0.753	deleterious	N	0.484869862	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.