TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15670	47233;47234;47235	chr2:178618450;178618449;178618448	chr2:179483177;179483176;179483175
N2AB	14029	42310;42311;42312	chr2:178618450;178618449;178618448	chr2:179483177;179483176;179483175
N2A	13102	39529;39530;39531	chr2:178618450;178618449;178618448	chr2:179483177;179483176;179483175
N2B	6605	20038;20039;20040	chr2:178618450;178618449;178618448	chr2:179483177;179483176;179483175
Novex-1	6730	20413;20414;20415	chr2:178618450;178618449;178618448	chr2:179483177;179483176;179483175
Novex-2	6797	20614;20615;20616	chr2:178618450;178618449;178618448	chr2:179483177;179483176;179483175
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Fn3-1
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.4866
• 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
F/I	None	None	0.012	N	0.156	0.079	0.247322355667	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
F/A	0.4567	ambiguous	0.3842	ambiguous	-1.314	Destabilizing	None	N	0.07	neutral	None	None	None	None	N
F/C	0.3964	ambiguous	0.3379	benign	-0.428	Destabilizing	0.56	D	0.283	neutral	N	0.469199012	None	None	N
F/D	0.7626	likely_pathogenic	0.7252	pathogenic	0.291	Stabilizing	0.072	N	0.351	neutral	None	None	None	None	N
F/E	0.7934	likely_pathogenic	0.7462	pathogenic	0.275	Stabilizing	0.072	N	0.28	neutral	None	None	None	None	N
F/G	0.7068	likely_pathogenic	0.6632	pathogenic	-1.546	Destabilizing	0.016	N	0.214	neutral	None	None	None	None	N
F/H	0.4959	ambiguous	0.4311	ambiguous	-0.178	Destabilizing	0.214	N	0.273	neutral	None	None	None	None	N
F/I	0.4422	ambiguous	0.4533	ambiguous	-0.695	Destabilizing	0.012	N	0.156	neutral	N	0.459456684	None	None	N
F/K	0.8151	likely_pathogenic	0.7311	pathogenic	-0.147	Destabilizing	0.072	N	0.284	neutral	None	None	None	None	N
F/L	0.8595	likely_pathogenic	0.8669	pathogenic	-0.695	Destabilizing	None	N	0.045	neutral	N	0.437424846	None	None	N
F/M	0.555	ambiguous	0.5514	ambiguous	-0.394	Destabilizing	0.12	N	0.254	neutral	None	None	None	None	N
F/N	0.5139	ambiguous	0.4449	ambiguous	0.058	Stabilizing	0.072	N	0.382	neutral	None	None	None	None	N
F/P	0.9933	likely_pathogenic	0.9908	pathogenic	-0.883	Destabilizing	0.136	N	0.363	neutral	None	None	None	None	N
F/Q	0.712	likely_pathogenic	0.6468	pathogenic	-0.135	Destabilizing	0.136	N	0.385	neutral	None	None	None	None	N
F/R	0.6957	likely_pathogenic	0.587	pathogenic	0.439	Stabilizing	0.136	N	0.365	neutral	None	None	None	None	N
F/S	0.3169	likely_benign	0.2756	benign	-0.721	Destabilizing	0.001	N	0.103	neutral	N	0.320591054	None	None	N
F/T	0.4654	ambiguous	0.3966	ambiguous	-0.644	Destabilizing	0.016	N	0.209	neutral	None	None	None	None	N
F/V	0.3439	ambiguous	0.3388	benign	-0.883	Destabilizing	0.012	N	0.247	neutral	N	0.443694667	None	None	N
F/W	0.4144	ambiguous	0.4166	ambiguous	-0.5	Destabilizing	0.356	N	0.305	neutral	None	None	None	None	N
F/Y	0.1127	likely_benign	0.1209	benign	-0.404	Destabilizing	None	N	0.043	neutral	N	0.429612827	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.