TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9167	27724;27725;27726	chr2:178712423;178712422;178712421	chr2:179577150;179577149;179577148
N2AB	8850	26773;26774;26775	chr2:178712423;178712422;178712421	chr2:179577150;179577149;179577148
N2A	7923	23992;23993;23994	chr2:178712423;178712422;178712421	chr2:179577150;179577149;179577148
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-77
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.0972
• 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
A/E	rs777165769	-2.006	0.934	N	0.76	0.206	0.301789629655	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
A/E	rs777165769	-2.006	0.934	N	0.76	0.206	0.301789629655	gnomAD-4.0.0	1.59121E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43279E-05	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
A/C	0.4551	ambiguous	0.4267	ambiguous	-0.866	Destabilizing	0.007	N	0.441	neutral	None	None	None	None	N
A/D	0.8684	likely_pathogenic	0.8736	pathogenic	-2.097	Highly Destabilizing	0.949	D	0.761	deleterious	None	None	None	None	N
A/E	0.82	likely_pathogenic	0.8194	pathogenic	-1.848	Destabilizing	0.934	D	0.76	deleterious	N	0.456541488	None	None	N
A/F	0.5755	likely_pathogenic	0.5447	ambiguous	-0.381	Destabilizing	0.974	D	0.764	deleterious	None	None	None	None	N
A/G	0.206	likely_benign	0.2035	benign	-1.3	Destabilizing	0.669	D	0.679	prob.neutral	N	0.45393896	None	None	N
A/H	0.8607	likely_pathogenic	0.8497	pathogenic	-1.922	Destabilizing	0.998	D	0.755	deleterious	None	None	None	None	N
A/I	0.3563	ambiguous	0.3293	benign	0.667	Stabilizing	0.949	D	0.763	deleterious	None	None	None	None	N
A/K	0.9342	likely_pathogenic	0.929	pathogenic	-0.678	Destabilizing	0.949	D	0.752	deleterious	None	None	None	None	N
A/L	0.3601	ambiguous	0.3242	benign	0.667	Stabilizing	0.728	D	0.719	prob.delet.	None	None	None	None	N
A/M	0.3691	ambiguous	0.3421	ambiguous	0.218	Stabilizing	0.998	D	0.735	prob.delet.	None	None	None	None	N
A/N	0.7151	likely_pathogenic	0.7011	pathogenic	-1.132	Destabilizing	0.949	D	0.758	deleterious	None	None	None	None	N
A/P	0.9519	likely_pathogenic	0.9476	pathogenic	0.23	Stabilizing	0.966	D	0.761	deleterious	N	0.458845666	None	None	N
A/Q	0.8154	likely_pathogenic	0.8038	pathogenic	-0.816	Destabilizing	0.974	D	0.767	deleterious	None	None	None	None	N
A/R	0.8759	likely_pathogenic	0.8707	pathogenic	-1.057	Destabilizing	0.949	D	0.771	deleterious	None	None	None	None	N
A/S	0.1382	likely_benign	0.1308	benign	-1.531	Destabilizing	0.022	N	0.456	neutral	N	0.425096133	None	None	N
A/T	0.1095	likely_benign	0.1041	benign	-1.139	Destabilizing	0.669	D	0.687	prob.neutral	N	0.493571996	None	None	N
A/V	0.162	likely_benign	0.1528	benign	0.23	Stabilizing	0.801	D	0.698	prob.neutral	N	0.50219148	None	None	N
A/W	0.9302	likely_pathogenic	0.9211	pathogenic	-1.249	Destabilizing	0.998	D	0.779	deleterious	None	None	None	None	N
A/Y	0.7723	likely_pathogenic	0.7574	pathogenic	-0.627	Destabilizing	0.991	D	0.765	deleterious	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.