TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22226	66901;66902;66903	chr2:178581592;178581591;178581590	chr2:179446319;179446318;179446317
N2AB	20585	61978;61979;61980	chr2:178581592;178581591;178581590	chr2:179446319;179446318;179446317
N2A	19658	59197;59198;59199	chr2:178581592;178581591;178581590	chr2:179446319;179446318;179446317
N2B	13161	39706;39707;39708	chr2:178581592;178581591;178581590	chr2:179446319;179446318;179446317
Novex-1	13286	40081;40082;40083	chr2:178581592;178581591;178581590	chr2:179446319;179446318;179446317
Novex-2	13353	40282;40283;40284	chr2:178581592;178581591;178581590	chr2:179446319;179446318;179446317
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: Fn3-49
• Domain position: 71
• Structural Position: 102
• Q(SASA): 0.1767
• 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	None	None	0.001	D	0.295	0.14	0.270001397563	gnomAD-4.0.0	1.20034E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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
T/A	0.1119	likely_benign	0.1011	benign	-0.974	Destabilizing	0.027	N	0.384	neutral	N	0.453224963	None	None	N
T/C	0.3957	ambiguous	0.3289	benign	-0.49	Destabilizing	0.824	D	0.368	neutral	None	None	None	None	N
T/D	0.6124	likely_pathogenic	0.5368	ambiguous	-1.065	Destabilizing	0.149	N	0.379	neutral	None	None	None	None	N
T/E	0.4217	ambiguous	0.3504	ambiguous	-0.897	Destabilizing	0.081	N	0.393	neutral	None	None	None	None	N
T/F	0.4108	ambiguous	0.3345	benign	-0.545	Destabilizing	0.38	N	0.429	neutral	None	None	None	None	N
T/G	0.3564	ambiguous	0.3276	benign	-1.378	Destabilizing	0.149	N	0.419	neutral	None	None	None	None	N
T/H	0.3703	ambiguous	0.3163	benign	-1.461	Destabilizing	0.824	D	0.414	neutral	None	None	None	None	N
T/I	0.2271	likely_benign	0.1898	benign	0.08	Stabilizing	0.001	N	0.295	neutral	D	0.522394259	None	None	N
T/K	0.3282	likely_benign	0.3047	benign	-0.637	Destabilizing	0.062	N	0.402	neutral	N	0.472426799	None	None	N
T/L	0.1779	likely_benign	0.1513	benign	0.08	Stabilizing	0.012	N	0.347	neutral	None	None	None	None	N
T/M	0.1479	likely_benign	0.1208	benign	0.119	Stabilizing	0.38	N	0.371	neutral	None	None	None	None	N
T/N	0.2152	likely_benign	0.1876	benign	-1.117	Destabilizing	0.38	N	0.393	neutral	None	None	None	None	N
T/P	0.7715	likely_pathogenic	0.7354	pathogenic	-0.24	Destabilizing	0.484	N	0.391	neutral	N	0.515096756	None	None	N
T/Q	0.2863	likely_benign	0.2521	benign	-0.919	Destabilizing	0.005	N	0.371	neutral	None	None	None	None	N
T/R	0.2907	likely_benign	0.2635	benign	-0.768	Destabilizing	0.188	N	0.394	neutral	N	0.495263586	None	None	N
T/S	0.1467	likely_benign	0.1353	benign	-1.359	Destabilizing	0.005	N	0.284	neutral	N	0.456553269	None	None	N
T/V	0.16	likely_benign	0.1404	benign	-0.24	Destabilizing	0.001	N	0.269	neutral	None	None	None	None	N
T/W	0.8246	likely_pathogenic	0.7503	pathogenic	-0.718	Destabilizing	0.935	D	0.507	neutral	None	None	None	None	N
T/Y	0.4253	ambiguous	0.3566	ambiguous	-0.371	Destabilizing	0.555	D	0.417	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.