TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9355	28288;28289;28290	chr2:178711173;178711172;178711171	chr2:179575900;179575899;179575898
N2AB	9038	27337;27338;27339	chr2:178711173;178711172;178711171	chr2:179575900;179575899;179575898
N2A	8111	24556;24557;24558	chr2:178711173;178711172;178711171	chr2:179575900;179575899;179575898
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-79
• Domain position: 55
• Structural Position: 135
• Q(SASA): 0.344
• 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/I	rs763942844	0.009	None	None	0.175	0.091	0.213573922156	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
T/I	rs763942844	0.009	None	None	0.175	0.091	0.213573922156	gnomAD-4.0.0	4.78929E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.29622E-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
T/A	0.0822	likely_benign	0.0904	benign	-0.857	Destabilizing	0.005	N	0.188	neutral	None	None	None	None	N
T/C	0.3698	ambiguous	0.4229	ambiguous	-0.726	Destabilizing	0.356	N	0.531	neutral	None	None	None	None	N
T/D	0.3643	ambiguous	0.4143	ambiguous	-1.341	Destabilizing	0.038	N	0.475	neutral	None	None	None	None	N
T/E	0.2357	likely_benign	0.2766	benign	-1.303	Destabilizing	0.072	N	0.474	neutral	None	None	None	None	N
T/F	0.1606	likely_benign	0.1855	benign	-1.013	Destabilizing	0.214	N	0.592	neutral	None	None	None	None	N
T/G	0.2464	likely_benign	0.2887	benign	-1.133	Destabilizing	0.031	N	0.479	neutral	None	None	None	None	N
T/H	0.1591	likely_benign	0.185	benign	-1.542	Destabilizing	0.356	N	0.551	neutral	None	None	None	None	N
T/I	0.0851	likely_benign	0.0925	benign	-0.201	Destabilizing	None	N	0.175	neutral	None	None	None	None	N
T/K	0.1052	likely_benign	0.1333	benign	-0.831	Destabilizing	0.055	N	0.471	neutral	None	None	None	None	N
T/L	0.0878	likely_benign	0.0938	benign	-0.201	Destabilizing	0.002	N	0.263	neutral	None	None	None	None	N
T/M	0.0793	likely_benign	0.0883	benign	0.192	Stabilizing	0.214	N	0.54	neutral	None	None	None	None	N
T/N	0.1131	likely_benign	0.1247	benign	-1.069	Destabilizing	0.001	N	0.117	neutral	None	None	None	None	N
T/P	0.5728	likely_pathogenic	0.6686	pathogenic	-0.388	Destabilizing	0.106	N	0.551	neutral	None	None	None	None	N
T/Q	0.1524	likely_benign	0.1845	benign	-1.26	Destabilizing	0.356	N	0.583	neutral	None	None	None	None	N
T/R	0.0812	likely_benign	0.1022	benign	-0.627	Destabilizing	0.106	N	0.573	neutral	None	None	None	None	N
T/S	0.1075	likely_benign	0.1191	benign	-1.192	Destabilizing	0.001	N	0.105	neutral	None	None	None	None	N
T/V	0.0803	likely_benign	0.0863	benign	-0.388	Destabilizing	None	N	0.116	neutral	None	None	None	None	N
T/W	0.4546	ambiguous	0.5507	ambiguous	-1.039	Destabilizing	0.864	D	0.561	neutral	None	None	None	None	N
T/Y	0.181	likely_benign	0.219	benign	-0.722	Destabilizing	0.356	N	0.575	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.