TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5218	15877;15878;15879	chr2:178733737;178733736;178733735	chr2:179598464;179598463;179598462
N2AB	4901	14926;14927;14928	chr2:178733737;178733736;178733735	chr2:179598464;179598463;179598462
N2A	3974	12145;12146;12147	chr2:178733737;178733736;178733735	chr2:179598464;179598463;179598462
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-35
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.3375
• 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/S	None	None	0.991	N	0.807	0.422	0.796026131282	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
F/V	rs1210028177	-1.093	0.939	N	0.724	0.414	0.718756738305	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
F/V	rs1210028177	-1.093	0.939	N	0.724	0.414	0.718756738305	gnomAD-4.0.0	1.20032E-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
F/A	0.7507	likely_pathogenic	0.8176	pathogenic	-1.433	Destabilizing	0.953	D	0.746	deleterious	None	None	None	None	N
F/C	0.473	ambiguous	0.5491	ambiguous	-0.769	Destabilizing	0.999	D	0.811	deleterious	D	0.545431868	None	None	N
F/D	0.9067	likely_pathogenic	0.9379	pathogenic	0.712	Stabilizing	0.998	D	0.83	deleterious	None	None	None	None	N
F/E	0.9308	likely_pathogenic	0.9462	pathogenic	0.743	Stabilizing	0.993	D	0.827	deleterious	None	None	None	None	N
F/G	0.8795	likely_pathogenic	0.9212	pathogenic	-1.685	Destabilizing	0.993	D	0.799	deleterious	None	None	None	None	N
F/H	0.6286	likely_pathogenic	0.6929	pathogenic	-0.131	Destabilizing	0.986	D	0.796	deleterious	None	None	None	None	N
F/I	0.2923	likely_benign	0.3437	ambiguous	-0.741	Destabilizing	0.982	D	0.751	deleterious	N	0.507893411	None	None	N
F/K	0.9213	likely_pathogenic	0.9436	pathogenic	-0.488	Destabilizing	0.993	D	0.827	deleterious	None	None	None	None	N
F/L	0.8618	likely_pathogenic	0.8946	pathogenic	-0.741	Destabilizing	0.885	D	0.629	neutral	N	0.509214071	None	None	N
F/M	0.6351	likely_pathogenic	0.6863	pathogenic	-0.611	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
F/N	0.7566	likely_pathogenic	0.8132	pathogenic	-0.457	Destabilizing	0.998	D	0.832	deleterious	None	None	None	None	N
F/P	0.9901	likely_pathogenic	0.9958	pathogenic	-0.955	Destabilizing	0.998	D	0.825	deleterious	None	None	None	None	N
F/Q	0.8668	likely_pathogenic	0.8967	pathogenic	-0.491	Destabilizing	0.998	D	0.829	deleterious	None	None	None	None	N
F/R	0.8382	likely_pathogenic	0.8789	pathogenic	0.019	Stabilizing	0.993	D	0.833	deleterious	None	None	None	None	N
F/S	0.5655	likely_pathogenic	0.6561	pathogenic	-1.302	Destabilizing	0.991	D	0.807	deleterious	N	0.484419953	None	None	N
F/T	0.6588	likely_pathogenic	0.7283	pathogenic	-1.183	Destabilizing	0.993	D	0.812	deleterious	None	None	None	None	N
F/V	0.2912	likely_benign	0.3413	ambiguous	-0.955	Destabilizing	0.939	D	0.724	prob.delet.	N	0.504805548	None	None	N
F/W	0.6247	likely_pathogenic	0.6745	pathogenic	-0.143	Destabilizing	0.998	D	0.74	deleterious	None	None	None	None	N
F/Y	0.1725	likely_benign	0.208	benign	-0.234	Destabilizing	0.046	N	0.373	neutral	N	0.445097862	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.