TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16184	48775;48776;48777	chr2:178615395;178615394;178615393	chr2:179480122;179480121;179480120
N2AB	14543	43852;43853;43854	chr2:178615395;178615394;178615393	chr2:179480122;179480121;179480120
N2A	13616	41071;41072;41073	chr2:178615395;178615394;178615393	chr2:179480122;179480121;179480120
N2B	7119	21580;21581;21582	chr2:178615395;178615394;178615393	chr2:179480122;179480121;179480120
Novex-1	7244	21955;21956;21957	chr2:178615395;178615394;178615393	chr2:179480122;179480121;179480120
Novex-2	7311	22156;22157;22158	chr2:178615395;178615394;178615393	chr2:179480122;179480121;179480120
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: Fn3-5
• Domain position: 30
• Structural Position: 32
• Q(SASA): 0.6273
• 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/A	None	None	1.0	D	0.611	0.466	0.421550847248	gnomAD-4.0.0	1.36929E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.32002E-05	0
G/V	None	None	1.0	D	0.781	0.548	0.918547691902	gnomAD-4.0.0	6.84643E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.16001E-05	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	0.7928	likely_pathogenic	0.7555	pathogenic	-0.074	Destabilizing	1.0	D	0.611	neutral	D	0.610667016	None	None	I
G/C	0.8552	likely_pathogenic	0.8011	pathogenic	-0.695	Destabilizing	1.0	D	0.781	deleterious	D	0.770155302	None	None	I
G/D	0.9328	likely_pathogenic	0.9103	pathogenic	-0.546	Destabilizing	1.0	D	0.684	prob.neutral	D	0.682059782	None	None	I
G/E	0.9593	likely_pathogenic	0.9447	pathogenic	-0.72	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
G/F	0.9672	likely_pathogenic	0.9563	pathogenic	-0.991	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
G/H	0.9484	likely_pathogenic	0.934	pathogenic	-0.309	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	I
G/I	0.9725	likely_pathogenic	0.9607	pathogenic	-0.354	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
G/K	0.9584	likely_pathogenic	0.9454	pathogenic	-0.423	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
G/L	0.9552	likely_pathogenic	0.9423	pathogenic	-0.354	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
G/M	0.9732	likely_pathogenic	0.9658	pathogenic	-0.315	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
G/N	0.8886	likely_pathogenic	0.8676	pathogenic	-0.108	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
G/P	0.9962	likely_pathogenic	0.9943	pathogenic	-0.234	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
G/Q	0.9321	likely_pathogenic	0.9129	pathogenic	-0.42	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	I
G/R	0.9078	likely_pathogenic	0.879	pathogenic	-0.022	Destabilizing	1.0	D	0.787	deleterious	D	0.684214052	None	None	I
G/S	0.627	likely_pathogenic	0.5702	pathogenic	-0.199	Destabilizing	1.0	D	0.694	prob.neutral	D	0.628163322	None	None	I
G/T	0.9103	likely_pathogenic	0.8835	pathogenic	-0.315	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
G/V	0.9518	likely_pathogenic	0.9332	pathogenic	-0.234	Destabilizing	1.0	D	0.781	deleterious	D	0.770155302	None	None	I
G/W	0.9603	likely_pathogenic	0.9426	pathogenic	-1.119	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
G/Y	0.9512	likely_pathogenic	0.9364	pathogenic	-0.756	Destabilizing	1.0	D	0.763	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.