TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21177	63754;63755;63756	chr2:178587780;178587779;178587778	chr2:179452507;179452506;179452505
N2AB	19536	58831;58832;58833	chr2:178587780;178587779;178587778	chr2:179452507;179452506;179452505
N2A	18609	56050;56051;56052	chr2:178587780;178587779;178587778	chr2:179452507;179452506;179452505
N2B	12112	36559;36560;36561	chr2:178587780;178587779;178587778	chr2:179452507;179452506;179452505
Novex-1	12237	36934;36935;36936	chr2:178587780;178587779;178587778	chr2:179452507;179452506;179452505
Novex-2	12304	37135;37136;37137	chr2:178587780;178587779;178587778	chr2:179452507;179452506;179452505
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-123
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.3757
• 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
D/E	rs879247635	None	0.993	N	0.503	0.324	0.402326594622	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
D/E	rs879247635	None	0.993	N	0.503	0.324	0.402326594622	gnomAD-4.0.0	6.57661E-06	None	None	None	None	N	None	2.41243E-05	0	None	0	0	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
D/A	0.8249	likely_pathogenic	0.8053	pathogenic	-0.239	Destabilizing	0.958	D	0.65	neutral	D	0.528240715	None	None	N
D/C	0.9741	likely_pathogenic	0.9719	pathogenic	-0.101	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
D/E	0.8259	likely_pathogenic	0.8117	pathogenic	-0.203	Destabilizing	0.993	D	0.503	neutral	N	0.513589045	None	None	N
D/F	0.9811	likely_pathogenic	0.9771	pathogenic	-0.108	Destabilizing	0.991	D	0.792	deleterious	None	None	None	None	N
D/G	0.8578	likely_pathogenic	0.8528	pathogenic	-0.42	Destabilizing	0.994	D	0.713	prob.delet.	D	0.529508162	None	None	N
D/H	0.906	likely_pathogenic	0.8826	pathogenic	0.282	Stabilizing	0.999	D	0.761	deleterious	D	0.529761652	None	None	N
D/I	0.9673	likely_pathogenic	0.9591	pathogenic	0.186	Stabilizing	0.334	N	0.513	neutral	None	None	None	None	N
D/K	0.9737	likely_pathogenic	0.9691	pathogenic	0.335	Stabilizing	0.995	D	0.761	deleterious	None	None	None	None	N
D/L	0.9188	likely_pathogenic	0.9046	pathogenic	0.186	Stabilizing	0.839	D	0.679	prob.neutral	None	None	None	None	N
D/M	0.9817	likely_pathogenic	0.9778	pathogenic	0.159	Stabilizing	0.998	D	0.806	deleterious	None	None	None	None	N
D/N	0.75	likely_pathogenic	0.7271	pathogenic	-0.012	Destabilizing	0.998	D	0.709	prob.delet.	D	0.528494204	None	None	N
D/P	0.9297	likely_pathogenic	0.9218	pathogenic	0.065	Stabilizing	0.998	D	0.763	deleterious	None	None	None	None	N
D/Q	0.9492	likely_pathogenic	0.9452	pathogenic	0.038	Stabilizing	0.998	D	0.753	deleterious	None	None	None	None	N
D/R	0.9691	likely_pathogenic	0.9654	pathogenic	0.591	Stabilizing	0.998	D	0.777	deleterious	None	None	None	None	N
D/S	0.7485	likely_pathogenic	0.7292	pathogenic	-0.119	Destabilizing	0.995	D	0.711	prob.delet.	None	None	None	None	N
D/T	0.9173	likely_pathogenic	0.9088	pathogenic	0.032	Stabilizing	0.991	D	0.729	prob.delet.	None	None	None	None	N
D/V	0.8957	likely_pathogenic	0.8755	pathogenic	0.065	Stabilizing	0.797	D	0.675	neutral	D	0.529001183	None	None	N
D/W	0.9951	likely_pathogenic	0.9943	pathogenic	0.036	Stabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
D/Y	0.8805	likely_pathogenic	0.8539	pathogenic	0.137	Stabilizing	0.998	D	0.782	deleterious	D	0.530015141	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.