TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26307	79144;79145;79146	chr2:178567213;178567212;178567211	chr2:179431940;179431939;179431938
N2AB	24666	74221;74222;74223	chr2:178567213;178567212;178567211	chr2:179431940;179431939;179431938
N2A	23739	71440;71441;71442	chr2:178567213;178567212;178567211	chr2:179431940;179431939;179431938
N2B	17242	51949;51950;51951	chr2:178567213;178567212;178567211	chr2:179431940;179431939;179431938
Novex-1	17367	52324;52325;52326	chr2:178567213;178567212;178567211	chr2:179431940;179431939;179431938
Novex-2	17434	52525;52526;52527	chr2:178567213;178567212;178567211	chr2:179431940;179431939;179431938
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: Fn3-79
• Domain position: 22
• Structural Position: 23
• Q(SASA): 0.265
• 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	0.055	N	0.445	0.183	0.376745185316	gnomAD-4.0.0	1.59938E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8732E-06	0	0
T/R	None	None	None	N	0.275	0.212	0.481616744073	gnomAD-4.0.0	1.59938E-06	None	None	None	None	N	None	0	0	None	0	2.77701E-05	None	0	0	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	0.0582	likely_benign	0.0623	benign	-1.131	Destabilizing	None	N	0.132	neutral	N	0.438847369	None	None	N
T/C	0.2314	likely_benign	0.2412	benign	-0.779	Destabilizing	0.356	N	0.503	neutral	None	None	None	None	N
T/D	0.3961	ambiguous	0.3988	ambiguous	-0.724	Destabilizing	0.072	N	0.416	neutral	None	None	None	None	N
T/E	0.3204	likely_benign	0.3156	benign	-0.615	Destabilizing	0.031	N	0.368	neutral	None	None	None	None	N
T/F	0.1348	likely_benign	0.1404	benign	-0.976	Destabilizing	0.356	N	0.569	neutral	None	None	None	None	N
T/G	0.1476	likely_benign	0.1667	benign	-1.49	Destabilizing	0.016	N	0.434	neutral	None	None	None	None	N
T/H	0.1748	likely_benign	0.1747	benign	-1.694	Destabilizing	0.356	N	0.562	neutral	None	None	None	None	N
T/I	0.1073	likely_benign	0.1097	benign	-0.226	Destabilizing	0.055	N	0.445	neutral	N	0.514673279	None	None	N
T/K	0.2195	likely_benign	0.2263	benign	-0.68	Destabilizing	0.012	N	0.37	neutral	N	0.490217552	None	None	N
T/L	0.0666	likely_benign	0.0709	benign	-0.226	Destabilizing	0.016	N	0.351	neutral	None	None	None	None	N
T/M	0.0738	likely_benign	0.0747	benign	-0.075	Destabilizing	0.356	N	0.498	neutral	None	None	None	None	N
T/N	0.0995	likely_benign	0.1028	benign	-0.996	Destabilizing	0.038	N	0.3	neutral	None	None	None	None	N
T/P	0.7157	likely_pathogenic	0.7707	pathogenic	-0.495	Destabilizing	0.055	N	0.442	neutral	N	0.504769819	None	None	N
T/Q	0.1797	likely_benign	0.1834	benign	-0.967	Destabilizing	0.072	N	0.461	neutral	None	None	None	None	N
T/R	0.1795	likely_benign	0.1836	benign	-0.679	Destabilizing	None	N	0.275	neutral	N	0.48673453	None	None	N
T/S	0.067	likely_benign	0.0683	benign	-1.304	Destabilizing	None	N	0.159	neutral	N	0.370520648	None	None	N
T/V	0.0891	likely_benign	0.093	benign	-0.495	Destabilizing	0.016	N	0.272	neutral	None	None	None	None	N
T/W	0.4363	ambiguous	0.4358	ambiguous	-0.962	Destabilizing	0.864	D	0.598	neutral	None	None	None	None	N
T/Y	0.1841	likely_benign	0.1916	benign	-0.669	Destabilizing	0.356	N	0.555	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.