TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	968	3127;3128;3129	chr2:178783004;178783003;178783002	chr2:179647731;179647730;179647729
N2AB	968	3127;3128;3129	chr2:178783004;178783003;178783002	chr2:179647731;179647730;179647729
N2A	968	3127;3128;3129	chr2:178783004;178783003;178783002	chr2:179647731;179647730;179647729
N2B	922	2989;2990;2991	chr2:178783004;178783003;178783002	chr2:179647731;179647730;179647729
Novex-1	922	2989;2990;2991	chr2:178783004;178783003;178783002	chr2:179647731;179647730;179647729
Novex-2	922	2989;2990;2991	chr2:178783004;178783003;178783002	chr2:179647731;179647730;179647729
Novex-3	968	3127;3128;3129	chr2:178783004;178783003;178783002	chr2:179647731;179647730;179647729

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-3
• Domain position: 26
• Structural Position: 40
• Q(SASA): 0.2784
• 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/E	None	None	0.999	D	0.793	0.693	0.795966037868	gnomAD-4.0.0	6.84079E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15931E-05	0
G/V	None	None	0.997	D	0.789	0.69	0.923725460125	gnomAD-4.0.0	6.84079E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99308E-07	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	0.8851	likely_pathogenic	0.9217	pathogenic	-0.503	Destabilizing	0.604	D	0.541	neutral	D	0.535286021	None	None	I
G/C	0.9847	likely_pathogenic	0.9915	pathogenic	-0.865	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
G/D	0.9933	likely_pathogenic	0.9964	pathogenic	-0.438	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	I
G/E	0.9962	likely_pathogenic	0.9981	pathogenic	-0.549	Destabilizing	0.999	D	0.793	deleterious	D	0.737670221	None	None	I
G/F	0.9984	likely_pathogenic	0.9991	pathogenic	-1.015	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
G/H	0.9986	likely_pathogenic	0.9993	pathogenic	-0.964	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
G/I	0.9952	likely_pathogenic	0.9975	pathogenic	-0.364	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
G/K	0.9989	likely_pathogenic	0.9995	pathogenic	-0.989	Destabilizing	0.999	D	0.798	deleterious	None	None	None	None	I
G/L	0.9964	likely_pathogenic	0.998	pathogenic	-0.364	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	I
G/M	0.9988	likely_pathogenic	0.9994	pathogenic	-0.402	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
G/N	0.9952	likely_pathogenic	0.9975	pathogenic	-0.597	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	I
G/P	0.9987	likely_pathogenic	0.9993	pathogenic	-0.372	Destabilizing	0.999	D	0.786	deleterious	None	None	None	None	I
G/Q	0.9974	likely_pathogenic	0.9987	pathogenic	-0.794	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
G/R	0.9937	likely_pathogenic	0.997	pathogenic	-0.666	Destabilizing	0.999	D	0.784	deleterious	D	0.803632429	None	None	I
G/S	0.8623	likely_pathogenic	0.9164	pathogenic	-0.852	Destabilizing	0.998	D	0.803	deleterious	None	None	None	None	I
G/T	0.9847	likely_pathogenic	0.9919	pathogenic	-0.875	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	I
G/V	0.9886	likely_pathogenic	0.9936	pathogenic	-0.372	Destabilizing	0.997	D	0.789	deleterious	D	0.747804547	None	None	I
G/W	0.9967	likely_pathogenic	0.9984	pathogenic	-1.265	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
G/Y	0.9982	likely_pathogenic	0.9991	pathogenic	-0.876	Destabilizing	1.0	D	0.779	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.