TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14560	43903;43904;43905	chr2:178632216;178632215;178632214	chr2:179496943;179496942;179496941
N2AB	12919	38980;38981;38982	chr2:178632216;178632215;178632214	chr2:179496943;179496942;179496941
N2A	11992	36199;36200;36201	chr2:178632216;178632215;178632214	chr2:179496943;179496942;179496941
N2B	5495	16708;16709;16710	chr2:178632216;178632215;178632214	chr2:179496943;179496942;179496941
Novex-1	5620	17083;17084;17085	chr2:178632216;178632215;178632214	chr2:179496943;179496942;179496941
Novex-2	5687	17284;17285;17286	chr2:178632216;178632215;178632214	chr2:179496943;179496942;179496941
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-96
• Domain position: 64
• Structural Position: 146
• Q(SASA): 0.4647
• 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
I/V	rs2059893136	None	0.001	N	0.18	0.174	0.278143212241	gnomAD-4.0.0	4.80815E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.41023E-06	1.17448E-05	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
I/A	0.1723	likely_benign	0.1501	benign	-0.905	Destabilizing	0.116	N	0.297	neutral	None	None	None	None	N
I/C	0.7293	likely_pathogenic	0.6785	pathogenic	-0.532	Destabilizing	0.981	D	0.292	neutral	None	None	None	None	N
I/D	0.6373	likely_pathogenic	0.5876	pathogenic	-0.496	Destabilizing	0.932	D	0.398	neutral	None	None	None	None	N
I/E	0.4548	ambiguous	0.4057	ambiguous	-0.596	Destabilizing	0.818	D	0.411	neutral	None	None	None	None	N
I/F	0.1652	likely_benign	0.1314	benign	-0.966	Destabilizing	0.457	N	0.256	neutral	N	0.505093023	None	None	N
I/G	0.5468	ambiguous	0.4676	ambiguous	-1.092	Destabilizing	0.818	D	0.401	neutral	None	None	None	None	N
I/H	0.5152	ambiguous	0.4467	ambiguous	-0.421	Destabilizing	0.981	D	0.386	neutral	None	None	None	None	N
I/K	0.2322	likely_benign	0.1975	benign	-0.429	Destabilizing	0.69	D	0.401	neutral	None	None	None	None	N
I/L	0.0828	likely_benign	0.0598	benign	-0.525	Destabilizing	0.001	N	0.156	neutral	N	0.34536699	None	None	N
I/M	0.0817	likely_benign	0.0702	benign	-0.305	Destabilizing	0.015	N	0.238	neutral	N	0.484473219	None	None	N
I/N	0.3163	likely_benign	0.2765	benign	-0.127	Destabilizing	0.773	D	0.381	neutral	D	0.545419883	None	None	N
I/P	0.4402	ambiguous	0.3714	ambiguous	-0.618	Destabilizing	0.932	D	0.391	neutral	None	None	None	None	N
I/Q	0.3895	ambiguous	0.3249	benign	-0.432	Destabilizing	0.818	D	0.382	neutral	None	None	None	None	N
I/R	0.1764	likely_benign	0.1592	benign	0.191	Stabilizing	0.69	D	0.391	neutral	None	None	None	None	N
I/S	0.2423	likely_benign	0.2204	benign	-0.597	Destabilizing	0.627	D	0.379	neutral	N	0.521204311	None	None	N
I/T	0.1101	likely_benign	0.1096	benign	-0.593	Destabilizing	0.324	N	0.337	neutral	D	0.532071396	None	None	N
I/V	0.0764	likely_benign	0.0713	benign	-0.618	Destabilizing	0.001	N	0.18	neutral	N	0.488711646	None	None	N
I/W	0.6741	likely_pathogenic	0.5795	pathogenic	-0.959	Destabilizing	0.981	D	0.451	neutral	None	None	None	None	N
I/Y	0.5144	ambiguous	0.4304	ambiguous	-0.699	Destabilizing	0.818	D	0.283	neutral	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.