TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28837	86734;86735;86736	chr2:178559623;178559622;178559621	chr2:179424350;179424349;179424348
N2AB	27196	81811;81812;81813	chr2:178559623;178559622;178559621	chr2:179424350;179424349;179424348
N2A	26269	79030;79031;79032	chr2:178559623;178559622;178559621	chr2:179424350;179424349;179424348
N2B	19772	59539;59540;59541	chr2:178559623;178559622;178559621	chr2:179424350;179424349;179424348
Novex-1	19897	59914;59915;59916	chr2:178559623;178559622;178559621	chr2:179424350;179424349;179424348
Novex-2	19964	60115;60116;60117	chr2:178559623;178559622;178559621	chr2:179424350;179424349;179424348
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-144
• Domain position: 83
• Structural Position: 171
• Q(SASA): 0.5746
• 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
T/S	None	None	0.992	N	0.492	0.245	0.335661160332	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/S	None	None	0.992	N	0.492	0.245	0.335661160332	gnomAD-4.0.0	6.56763E-06	None	None	None	None	N	None	2.40616E-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
T/A	0.1214	likely_benign	0.1239	benign	-0.555	Destabilizing	0.767	D	0.343	neutral	N	0.482265364	None	None	N
T/C	0.51	ambiguous	0.5588	ambiguous	-0.367	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
T/D	0.6078	likely_pathogenic	0.5964	pathogenic	0.289	Stabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
T/E	0.5811	likely_pathogenic	0.5737	pathogenic	0.246	Stabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
T/F	0.2975	likely_benign	0.3098	benign	-0.886	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
T/G	0.3408	ambiguous	0.3541	ambiguous	-0.739	Destabilizing	0.997	D	0.691	prob.neutral	None	None	None	None	N
T/H	0.3288	likely_benign	0.3423	ambiguous	-0.988	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
T/I	0.2299	likely_benign	0.2509	benign	-0.18	Destabilizing	0.999	D	0.768	deleterious	D	0.536638567	None	None	N
T/K	0.5177	ambiguous	0.5119	ambiguous	-0.438	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
T/L	0.145	likely_benign	0.1497	benign	-0.18	Destabilizing	0.997	D	0.639	neutral	None	None	None	None	N
T/M	0.1014	likely_benign	0.1048	benign	-0.018	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
T/N	0.1413	likely_benign	0.1476	benign	-0.294	Destabilizing	1.0	D	0.695	prob.neutral	N	0.498946971	None	None	N
T/P	0.1429	likely_benign	0.1249	benign	-0.274	Destabilizing	0.999	D	0.775	deleterious	N	0.492773582	None	None	N
T/Q	0.3368	likely_benign	0.3372	benign	-0.472	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
T/R	0.464	ambiguous	0.457	ambiguous	-0.197	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
T/S	0.1181	likely_benign	0.1217	benign	-0.574	Destabilizing	0.992	D	0.492	neutral	N	0.455558766	None	None	N
T/V	0.175	likely_benign	0.1882	benign	-0.274	Destabilizing	0.997	D	0.535	neutral	None	None	None	None	N
T/W	0.7253	likely_pathogenic	0.7374	pathogenic	-0.847	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
T/Y	0.3771	ambiguous	0.3886	ambiguous	-0.582	Destabilizing	1.0	D	0.794	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.