TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30014	90265;90266;90267	chr2:178552860;178552859;178552858	chr2:179417587;179417586;179417585
N2AB	28373	85342;85343;85344	chr2:178552860;178552859;178552858	chr2:179417587;179417586;179417585
N2A	27446	82561;82562;82563	chr2:178552860;178552859;178552858	chr2:179417587;179417586;179417585
N2B	20949	63070;63071;63072	chr2:178552860;178552859;178552858	chr2:179417587;179417586;179417585
Novex-1	21074	63445;63446;63447	chr2:178552860;178552859;178552858	chr2:179417587;179417586;179417585
Novex-2	21141	63646;63647;63648	chr2:178552860;178552859;178552858	chr2:179417587;179417586;179417585
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-106
• Domain position: 82
• Structural Position: 115
• Q(SASA): 0.1672
• 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	rs1359003253	-0.753	1.0	D	0.896	0.742	0.828329613222	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	2.67E-05	0
G/E	rs1359003253	-0.753	1.0	D	0.896	0.742	0.828329613222	gnomAD-4.0.0	2.25791E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87823E-05	0	1.6564E-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	0.8923	likely_pathogenic	0.8264	pathogenic	-0.7	Destabilizing	1.0	D	0.745	deleterious	D	0.564025286	None	None	I
G/C	0.9581	likely_pathogenic	0.9286	pathogenic	-1.045	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	I
G/D	0.9754	likely_pathogenic	0.9612	pathogenic	-1.054	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	I
G/E	0.9874	likely_pathogenic	0.9789	pathogenic	-1.183	Destabilizing	1.0	D	0.896	deleterious	D	0.575381592	None	None	I
G/F	0.9942	likely_pathogenic	0.9905	pathogenic	-1.186	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	I
G/H	0.9932	likely_pathogenic	0.9886	pathogenic	-0.974	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
G/I	0.9942	likely_pathogenic	0.9894	pathogenic	-0.638	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	I
G/K	0.9932	likely_pathogenic	0.9888	pathogenic	-1.246	Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	I
G/L	0.991	likely_pathogenic	0.9862	pathogenic	-0.638	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	I
G/M	0.9953	likely_pathogenic	0.9918	pathogenic	-0.561	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
G/N	0.9816	likely_pathogenic	0.9724	pathogenic	-0.912	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
G/P	0.999	likely_pathogenic	0.9983	pathogenic	-0.622	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	I
G/Q	0.987	likely_pathogenic	0.9795	pathogenic	-1.206	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	I
G/R	0.979	likely_pathogenic	0.9656	pathogenic	-0.741	Destabilizing	1.0	D	0.905	deleterious	D	0.557695411	None	None	I
G/S	0.8096	likely_pathogenic	0.7273	pathogenic	-1.095	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
G/T	0.9663	likely_pathogenic	0.9472	pathogenic	-1.159	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	I
G/V	0.9879	likely_pathogenic	0.979	pathogenic	-0.622	Destabilizing	1.0	D	0.873	deleterious	D	0.541819655	None	None	I
G/W	0.9904	likely_pathogenic	0.9824	pathogenic	-1.364	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	I
G/Y	0.9911	likely_pathogenic	0.985	pathogenic	-1.038	Destabilizing	1.0	D	0.879	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.