TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15787	47584;47585;47586	chr2:178617992;178617991;178617990	chr2:179482719;179482718;179482717
N2AB	14146	42661;42662;42663	chr2:178617992;178617991;178617990	chr2:179482719;179482718;179482717
N2A	13219	39880;39881;39882	chr2:178617992;178617991;178617990	chr2:179482719;179482718;179482717
N2B	6722	20389;20390;20391	chr2:178617992;178617991;178617990	chr2:179482719;179482718;179482717
Novex-1	6847	20764;20765;20766	chr2:178617992;178617991;178617990	chr2:179482719;179482718;179482717
Novex-2	6914	20965;20966;20967	chr2:178617992;178617991;178617990	chr2:179482719;179482718;179482717
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-2
• Domain position: 30
• Structural Position: 32
• Q(SASA): 0.6061
• 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	rs2057660635	None	0.999	D	0.725	0.475	0.448498829774	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
G/S	rs2057660635	None	0.999	D	0.725	0.475	0.448498829774	gnomAD-4.0.0	6.20164E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	7.63281E-06	0	1.60277E-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
G/A	0.683	likely_pathogenic	0.7069	pathogenic	-0.249	Destabilizing	0.995	D	0.611	neutral	D	0.607279422	None	None	I
G/C	0.8095	likely_pathogenic	0.8339	pathogenic	-0.881	Destabilizing	1.0	D	0.83	deleterious	D	0.715751101	None	None	I
G/D	0.8243	likely_pathogenic	0.8447	pathogenic	-0.25	Destabilizing	0.604	D	0.579	neutral	D	0.674791697	None	None	I
G/E	0.8721	likely_pathogenic	0.8859	pathogenic	-0.4	Destabilizing	0.998	D	0.809	deleterious	None	None	None	None	I
G/F	0.9634	likely_pathogenic	0.9646	pathogenic	-0.897	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
G/H	0.9279	likely_pathogenic	0.9229	pathogenic	-0.421	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
G/I	0.957	likely_pathogenic	0.9628	pathogenic	-0.364	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
G/K	0.9165	likely_pathogenic	0.9151	pathogenic	-0.692	Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	I
G/L	0.9363	likely_pathogenic	0.9367	pathogenic	-0.364	Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	I
G/M	0.9486	likely_pathogenic	0.9432	pathogenic	-0.507	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
G/N	0.8316	likely_pathogenic	0.7976	pathogenic	-0.368	Destabilizing	0.998	D	0.731	prob.delet.	None	None	None	None	I
G/P	0.9956	likely_pathogenic	0.9962	pathogenic	-0.293	Destabilizing	0.999	D	0.819	deleterious	None	None	None	None	I
G/Q	0.8866	likely_pathogenic	0.8772	pathogenic	-0.608	Destabilizing	0.999	D	0.835	deleterious	None	None	None	None	I
G/R	0.8531	likely_pathogenic	0.8591	pathogenic	-0.297	Destabilizing	0.999	D	0.835	deleterious	D	0.619278622	None	None	I
G/S	0.5619	ambiguous	0.5684	pathogenic	-0.571	Destabilizing	0.999	D	0.725	prob.delet.	D	0.616455273	None	None	I
G/T	0.8821	likely_pathogenic	0.8891	pathogenic	-0.64	Destabilizing	0.999	D	0.814	deleterious	None	None	None	None	I
G/V	0.9287	likely_pathogenic	0.9422	pathogenic	-0.293	Destabilizing	0.999	D	0.827	deleterious	D	0.75204479	None	None	I
G/W	0.9568	likely_pathogenic	0.9593	pathogenic	-1.051	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
G/Y	0.9397	likely_pathogenic	0.9384	pathogenic	-0.699	Destabilizing	1.0	D	0.823	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.