TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8505	25738;25739;25740	chr2:178717221;178717220;178717219	chr2:179581948;179581947;179581946
N2AB	8188	24787;24788;24789	chr2:178717221;178717220;178717219	chr2:179581948;179581947;179581946
N2A	7261	22006;22007;22008	chr2:178717221;178717220;178717219	chr2:179581948;179581947;179581946
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: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-70
• Domain position: 50
• Structural Position: 125
• Q(SASA): 0.4798
• 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/A	rs1361103429	None	0.07	D	0.309	0.191	0.163833314356	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/A	rs1361103429	None	0.07	D	0.309	0.191	0.163833314356	gnomAD-4.0.0	1.23949E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.64366E-04	8.47683E-07	0	0
T/S	None	None	0.005	N	0.105	0.141	0.101711395817	gnomAD-4.0.0	6.84279E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	1.7337E-04	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	0.1045	likely_benign	0.1091	benign	-0.518	Destabilizing	0.07	N	0.309	neutral	D	0.531635392	None	None	N
T/C	0.6053	likely_pathogenic	0.637	pathogenic	-0.168	Destabilizing	0.998	D	0.421	neutral	None	None	None	None	N
T/D	0.4071	ambiguous	0.4284	ambiguous	-0.05	Destabilizing	0.84	D	0.396	neutral	None	None	None	None	N
T/E	0.3586	ambiguous	0.3741	ambiguous	-0.09	Destabilizing	0.833	D	0.363	neutral	None	None	None	None	N
T/F	0.2308	likely_benign	0.2684	benign	-0.73	Destabilizing	0.985	D	0.501	neutral	None	None	None	None	N
T/G	0.3116	likely_benign	0.3249	benign	-0.729	Destabilizing	0.862	D	0.401	neutral	None	None	None	None	N
T/H	0.2426	likely_benign	0.26	benign	-1.028	Destabilizing	0.998	D	0.483	neutral	None	None	None	None	N
T/I	0.2066	likely_benign	0.2225	benign	-0.062	Destabilizing	0.14	N	0.22	neutral	N	0.511646909	None	None	N
T/K	0.2817	likely_benign	0.2862	benign	-0.584	Destabilizing	0.874	D	0.353	neutral	None	None	None	None	N
T/L	0.1204	likely_benign	0.1334	benign	-0.062	Destabilizing	0.331	N	0.356	neutral	None	None	None	None	N
T/M	0.0885	likely_benign	0.0944	benign	0.181	Stabilizing	0.59	D	0.352	neutral	None	None	None	None	N
T/N	0.1178	likely_benign	0.1246	benign	-0.327	Destabilizing	0.798	D	0.345	neutral	N	0.489557578	None	None	N
T/P	0.6433	likely_pathogenic	0.6888	pathogenic	-0.183	Destabilizing	0.889	D	0.425	neutral	N	0.511713984	None	None	N
T/Q	0.2348	likely_benign	0.2456	benign	-0.519	Destabilizing	0.92	D	0.435	neutral	None	None	None	None	N
T/R	0.2403	likely_benign	0.2536	benign	-0.316	Destabilizing	0.985	D	0.423	neutral	None	None	None	None	N
T/S	0.1058	likely_benign	0.1105	benign	-0.547	Destabilizing	0.005	N	0.105	neutral	N	0.422294341	None	None	N
T/V	0.1721	likely_benign	0.1842	benign	-0.183	Destabilizing	0.063	N	0.182	neutral	None	None	None	None	N
T/W	0.6155	likely_pathogenic	0.665	pathogenic	-0.72	Destabilizing	0.999	D	0.525	neutral	None	None	None	None	N
T/Y	0.2839	likely_benign	0.3133	benign	-0.483	Destabilizing	0.992	D	0.502	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.