TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25949	78070;78071;78072	chr2:178568287;178568286;178568285	chr2:179433014;179433013;179433012
N2AB	24308	73147;73148;73149	chr2:178568287;178568286;178568285	chr2:179433014;179433013;179433012
N2A	23381	70366;70367;70368	chr2:178568287;178568286;178568285	chr2:179433014;179433013;179433012
N2B	16884	50875;50876;50877	chr2:178568287;178568286;178568285	chr2:179433014;179433013;179433012
Novex-1	17009	51250;51251;51252	chr2:178568287;178568286;178568285	chr2:179433014;179433013;179433012
Novex-2	17076	51451;51452;51453	chr2:178568287;178568286;178568285	chr2:179433014;179433013;179433012
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: Fn3-76
• Domain position: 60
• Structural Position: 90
• Q(SASA): 0.2637
• 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	rs1706723806	None	0.955	N	0.581	0.46	0.451407941134	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/I	rs1706723806	None	0.955	N	0.581	0.46	0.451407941134	gnomAD-4.0.0	6.57523E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47059E-05	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	0.106	likely_benign	0.1022	benign	-0.944	Destabilizing	0.955	D	0.459	neutral	N	0.477586983	None	None	N
T/C	0.4397	ambiguous	0.3848	ambiguous	-0.579	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
T/D	0.7077	likely_pathogenic	0.6969	pathogenic	-0.222	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
T/E	0.5518	ambiguous	0.5397	ambiguous	-0.125	Destabilizing	0.998	D	0.717	prob.delet.	None	None	None	None	N
T/F	0.3006	likely_benign	0.2601	benign	-0.802	Destabilizing	0.998	D	0.821	deleterious	None	None	None	None	N
T/G	0.361	ambiguous	0.3407	ambiguous	-1.292	Destabilizing	0.998	D	0.691	prob.neutral	None	None	None	None	N
T/H	0.3148	likely_benign	0.2987	benign	-1.437	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
T/I	0.2135	likely_benign	0.1687	benign	-0.079	Destabilizing	0.955	D	0.581	neutral	N	0.499351769	None	None	N
T/K	0.351	ambiguous	0.3467	ambiguous	-0.513	Destabilizing	0.997	D	0.738	prob.delet.	D	0.525735635	None	None	N
T/L	0.1302	likely_benign	0.1122	benign	-0.079	Destabilizing	0.966	D	0.473	neutral	None	None	None	None	N
T/M	0.087	likely_benign	0.0803	benign	-0.022	Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
T/N	0.1832	likely_benign	0.1658	benign	-0.764	Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	N
T/P	0.8476	likely_pathogenic	0.8597	pathogenic	-0.334	Destabilizing	0.999	D	0.768	deleterious	N	0.50271913	None	None	N
T/Q	0.2791	likely_benign	0.2679	benign	-0.714	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
T/R	0.3141	likely_benign	0.3109	benign	-0.505	Destabilizing	0.997	D	0.791	deleterious	N	0.466444487	None	None	N
T/S	0.1144	likely_benign	0.1099	benign	-1.107	Destabilizing	0.989	D	0.44	neutral	N	0.438767224	None	None	N
T/V	0.139	likely_benign	0.1167	benign	-0.334	Destabilizing	0.15	N	0.419	neutral	None	None	None	None	N
T/W	0.7574	likely_pathogenic	0.7312	pathogenic	-0.794	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
T/Y	0.3922	ambiguous	0.3612	ambiguous	-0.498	Destabilizing	0.999	D	0.825	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.