TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7016	21271;21272;21273	chr2:178724329;178724328;178724327	chr2:179589056;179589055;179589054
N2AB	6699	20320;20321;20322	chr2:178724329;178724328;178724327	chr2:179589056;179589055;179589054
N2A	5772	17539;17540;17541	chr2:178724329;178724328;178724327	chr2:179589056;179589055;179589054
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: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-54
• Domain position: 69
• Structural Position: 152
• Q(SASA): 0.1849
• Predicted PPI site: I

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
G/S	rs2078965197	None	1.0	D	0.853	0.61	0.570825458115	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
G/S	rs2078965197	None	1.0	D	0.853	0.61	0.570825458115	gnomAD-4.0.0	2.56295E-06	None	None	None	None	I	None	3.38318E-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
G/A	0.4711	ambiguous	0.4054	ambiguous	-0.685	Destabilizing	1.0	D	0.781	deleterious	D	0.56912978	None	None	I
G/C	0.8995	likely_pathogenic	0.8667	pathogenic	-0.86	Destabilizing	1.0	D	0.748	deleterious	D	0.640211447	None	None	I
G/D	0.9281	likely_pathogenic	0.8866	pathogenic	-0.995	Destabilizing	1.0	D	0.836	deleterious	D	0.639807839	None	None	I
G/E	0.9617	likely_pathogenic	0.9406	pathogenic	-1.052	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
G/F	0.9906	likely_pathogenic	0.9867	pathogenic	-1.075	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
G/H	0.9884	likely_pathogenic	0.9793	pathogenic	-1.307	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
G/I	0.9879	likely_pathogenic	0.9816	pathogenic	-0.304	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	I
G/K	0.9841	likely_pathogenic	0.9725	pathogenic	-1.142	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
G/L	0.9816	likely_pathogenic	0.9727	pathogenic	-0.304	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	I
G/M	0.9865	likely_pathogenic	0.9796	pathogenic	-0.237	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
G/N	0.9633	likely_pathogenic	0.9333	pathogenic	-0.846	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
G/P	0.9982	likely_pathogenic	0.9974	pathogenic	-0.389	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
G/Q	0.9686	likely_pathogenic	0.9477	pathogenic	-1.009	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
G/R	0.9566	likely_pathogenic	0.9312	pathogenic	-0.85	Destabilizing	1.0	D	0.808	deleterious	D	0.640009643	None	None	I
G/S	0.5691	likely_pathogenic	0.4556	ambiguous	-1.122	Destabilizing	1.0	D	0.853	deleterious	D	0.602227526	None	None	I
G/T	0.9338	likely_pathogenic	0.8885	pathogenic	-1.091	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
G/V	0.9601	likely_pathogenic	0.9423	pathogenic	-0.389	Destabilizing	1.0	D	0.764	deleterious	D	0.624192086	None	None	I
G/W	0.9901	likely_pathogenic	0.9845	pathogenic	-1.445	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
G/Y	0.9895	likely_pathogenic	0.9854	pathogenic	-1.005	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	I

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.