TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17904	53935;53936;53937	chr2:178605585;178605584;178605583	chr2:179470312;179470311;179470310
N2AB	16263	49012;49013;49014	chr2:178605585;178605584;178605583	chr2:179470312;179470311;179470310
N2A	15336	46231;46232;46233	chr2:178605585;178605584;178605583	chr2:179470312;179470311;179470310
N2B	8839	26740;26741;26742	chr2:178605585;178605584;178605583	chr2:179470312;179470311;179470310
Novex-1	8964	27115;27116;27117	chr2:178605585;178605584;178605583	chr2:179470312;179470311;179470310
Novex-2	9031	27316;27317;27318	chr2:178605585;178605584;178605583	chr2:179470312;179470311;179470310
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-18
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.5031
• 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
H/Q	rs2054588188	None	0.016	N	0.127	0.163	0.0297737177859	gnomAD-4.0.0	1.59435E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.03049E-05

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
H/A	0.3953	ambiguous	0.4342	ambiguous	0.535	Stabilizing	0.345	N	0.477	neutral	None	None	None	None	N
H/C	0.3653	ambiguous	0.3844	ambiguous	1.274	Stabilizing	0.991	D	0.496	neutral	None	None	None	None	N
H/D	0.5128	ambiguous	0.5867	pathogenic	0.232	Stabilizing	0.491	N	0.407	neutral	N	0.391898784	None	None	N
H/E	0.4916	ambiguous	0.5559	ambiguous	0.259	Stabilizing	0.209	N	0.272	neutral	None	None	None	None	N
H/F	0.3606	ambiguous	0.4306	ambiguous	1.088	Stabilizing	0.818	D	0.46	neutral	None	None	None	None	N
H/G	0.4812	ambiguous	0.528	ambiguous	0.232	Stabilizing	0.722	D	0.484	neutral	None	None	None	None	N
H/I	0.4198	ambiguous	0.5017	ambiguous	1.309	Stabilizing	0.39	N	0.548	neutral	None	None	None	None	N
H/K	0.3663	ambiguous	0.3928	ambiguous	0.643	Stabilizing	0.209	N	0.419	neutral	None	None	None	None	N
H/L	0.1814	likely_benign	0.2321	benign	1.309	Stabilizing	0.001	N	0.296	neutral	N	0.372504947	None	None	N
H/M	0.4908	ambiguous	0.5344	ambiguous	1.136	Stabilizing	0.818	D	0.503	neutral	None	None	None	None	N
H/N	0.1791	likely_benign	0.2141	benign	0.823	Stabilizing	0.662	D	0.268	neutral	N	0.382607297	None	None	N
H/P	0.2943	likely_benign	0.3025	benign	1.078	Stabilizing	0.001	N	0.285	neutral	N	0.384050092	None	None	N
H/Q	0.2507	likely_benign	0.292	benign	0.926	Stabilizing	0.016	N	0.127	neutral	N	0.36665641	None	None	N
H/R	0.2045	likely_benign	0.2382	benign	-0.079	Destabilizing	0.491	N	0.249	neutral	N	0.41054326	None	None	N
H/S	0.3664	ambiguous	0.4085	ambiguous	0.965	Stabilizing	0.345	N	0.417	neutral	None	None	None	None	N
H/T	0.4403	ambiguous	0.4896	ambiguous	1.086	Stabilizing	0.561	D	0.489	neutral	None	None	None	None	N
H/V	0.3737	ambiguous	0.4326	ambiguous	1.078	Stabilizing	0.39	N	0.507	neutral	None	None	None	None	N
H/W	0.4455	ambiguous	0.5008	ambiguous	1.02	Stabilizing	0.991	D	0.495	neutral	None	None	None	None	N
H/Y	0.1523	likely_benign	0.1881	benign	1.379	Stabilizing	0.662	D	0.344	neutral	N	0.433593478	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.