TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9921	29986;29987;29988	chr2:178704711;178704710;178704709	chr2:179569438;179569437;179569436
N2AB	9604	29035;29036;29037	chr2:178704711;178704710;178704709	chr2:179569438;179569437;179569436
N2A	8677	26254;26255;26256	chr2:178704711;178704710;178704709	chr2:179569438;179569437;179569436
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-84
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.0843
• 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
I/T	rs373651676	-3.671	0.425	None	0.656	0.17	None	gnomAD-2.1.1	3.97E-05	None	None	None	None	N	None	0	0	None	0	0	None	3.29E-05	None	0	7.88E-05	0
I/T	rs373651676	-3.671	0.425	None	0.656	0.17	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
I/T	rs373651676	-3.671	0.425	None	0.656	0.17	None	gnomAD-4.0.0	4.34417E-05	None	None	None	None	N	None	0	0	None	6.7627E-05	0	None	0	0	5.51147E-05	1.09946E-05	3.20554E-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
I/A	0.6278	likely_pathogenic	0.5959	pathogenic	-2.953	Highly Destabilizing	0.176	N	0.595	neutral	None	None	None	None	N
I/C	0.7663	likely_pathogenic	0.813	pathogenic	-2.38	Highly Destabilizing	0.001	N	0.544	neutral	None	None	None	None	N
I/D	0.9962	likely_pathogenic	0.989	pathogenic	-3.752	Highly Destabilizing	0.981	D	0.797	deleterious	None	None	None	None	N
I/E	0.9901	likely_pathogenic	0.9739	pathogenic	-3.461	Highly Destabilizing	0.981	D	0.799	deleterious	None	None	None	None	N
I/F	0.8482	likely_pathogenic	0.7461	pathogenic	-1.67	Destabilizing	0.784	D	0.691	prob.neutral	None	None	None	None	N
I/G	0.9548	likely_pathogenic	0.9359	pathogenic	-3.525	Highly Destabilizing	0.828	D	0.739	prob.delet.	None	None	None	None	N
I/H	0.9954	likely_pathogenic	0.9889	pathogenic	-3.128	Highly Destabilizing	0.995	D	0.811	deleterious	None	None	None	None	N
I/K	0.9908	likely_pathogenic	0.9706	pathogenic	-2.372	Highly Destabilizing	0.936	D	0.785	deleterious	None	None	None	None	N
I/L	0.4306	ambiguous	0.4067	ambiguous	-1.23	Destabilizing	0.139	N	0.415	neutral	None	None	None	None	N
I/M	0.2375	likely_benign	0.2019	benign	-1.447	Destabilizing	0.927	D	0.644	neutral	None	None	None	None	N
I/N	0.9496	likely_pathogenic	0.8996	pathogenic	-3.001	Highly Destabilizing	0.975	D	0.812	deleterious	None	None	None	None	N
I/P	0.9983	likely_pathogenic	0.9947	pathogenic	-1.796	Destabilizing	0.981	D	0.801	deleterious	None	None	None	None	N
I/Q	0.9893	likely_pathogenic	0.9747	pathogenic	-2.713	Highly Destabilizing	0.981	D	0.811	deleterious	None	None	None	None	N
I/R	0.9867	likely_pathogenic	0.9609	pathogenic	-2.227	Highly Destabilizing	0.981	D	0.808	deleterious	None	None	None	None	N
I/S	0.858	likely_pathogenic	0.7991	pathogenic	-3.564	Highly Destabilizing	0.642	D	0.71	prob.delet.	None	None	None	None	N
I/T	0.5917	likely_pathogenic	0.4949	ambiguous	-3.128	Highly Destabilizing	0.425	N	0.656	neutral	None	None	None	None	N
I/V	0.1482	likely_benign	0.1586	benign	-1.796	Destabilizing	0.01	N	0.307	neutral	None	None	None	None	N
I/W	0.9963	likely_pathogenic	0.9889	pathogenic	-2.171	Highly Destabilizing	0.995	D	0.806	deleterious	None	None	None	None	N
I/Y	0.9828	likely_pathogenic	0.9552	pathogenic	-1.996	Destabilizing	0.981	D	0.767	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.