TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20742	62449;62450;62451	chr2:178589501;178589500;178589499	chr2:179454228;179454227;179454226
N2AB	19101	57526;57527;57528	chr2:178589501;178589500;178589499	chr2:179454228;179454227;179454226
N2A	18174	54745;54746;54747	chr2:178589501;178589500;178589499	chr2:179454228;179454227;179454226
N2B	11677	35254;35255;35256	chr2:178589501;178589500;178589499	chr2:179454228;179454227;179454226
Novex-1	11802	35629;35630;35631	chr2:178589501;178589500;178589499	chr2:179454228;179454227;179454226
Novex-2	11869	35830;35831;35832	chr2:178589501;178589500;178589499	chr2:179454228;179454227;179454226
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-38
• Domain position: 75
• Structural Position: 107
• Q(SASA): 0.123
• Predicted PPI site: N

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
R/G	None	None	0.978	D	0.552	0.521	0.478376075226	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.09898E-04

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
R/A	0.9795	likely_pathogenic	0.9756	pathogenic	-2.202	Highly Destabilizing	0.923	D	0.575	neutral	None	None	None	None	N
R/C	0.7394	likely_pathogenic	0.7321	pathogenic	-1.991	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
R/D	0.9991	likely_pathogenic	0.9987	pathogenic	-1.62	Destabilizing	0.995	D	0.58	neutral	None	None	None	None	N
R/E	0.9847	likely_pathogenic	0.9786	pathogenic	-1.418	Destabilizing	0.983	D	0.538	neutral	None	None	None	None	N
R/F	0.9942	likely_pathogenic	0.992	pathogenic	-1.188	Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
R/G	0.9818	likely_pathogenic	0.9806	pathogenic	-2.468	Highly Destabilizing	0.978	D	0.552	neutral	D	0.524359012	None	None	N
R/H	0.7145	likely_pathogenic	0.6455	pathogenic	-2.087	Highly Destabilizing	0.999	D	0.571	neutral	None	None	None	None	N
R/I	0.9699	likely_pathogenic	0.9702	pathogenic	-1.397	Destabilizing	0.997	D	0.718	prob.delet.	D	0.524359012	None	None	N
R/K	0.5583	ambiguous	0.5706	pathogenic	-1.438	Destabilizing	0.948	D	0.626	neutral	N	0.478120415	None	None	N
R/L	0.9514	likely_pathogenic	0.9469	pathogenic	-1.397	Destabilizing	0.983	D	0.557	neutral	None	None	None	None	N
R/M	0.9743	likely_pathogenic	0.9716	pathogenic	-1.875	Destabilizing	1.0	D	0.615	neutral	None	None	None	None	N
R/N	0.9963	likely_pathogenic	0.9944	pathogenic	-1.762	Destabilizing	0.983	D	0.519	neutral	None	None	None	None	N
R/P	0.9997	likely_pathogenic	0.9996	pathogenic	-1.662	Destabilizing	0.998	D	0.661	neutral	None	None	None	None	N
R/Q	0.6643	likely_pathogenic	0.5909	pathogenic	-1.479	Destabilizing	0.998	D	0.528	neutral	None	None	None	None	N
R/S	0.9924	likely_pathogenic	0.9898	pathogenic	-2.369	Highly Destabilizing	0.37	N	0.489	neutral	N	0.509707343	None	None	N
R/T	0.9885	likely_pathogenic	0.9857	pathogenic	-2.0	Highly Destabilizing	0.956	D	0.523	neutral	N	0.498946922	None	None	N
R/V	0.9736	likely_pathogenic	0.9721	pathogenic	-1.662	Destabilizing	0.995	D	0.684	prob.neutral	None	None	None	None	N
R/W	0.9392	likely_pathogenic	0.9124	pathogenic	-0.861	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	N
R/Y	0.9819	likely_pathogenic	0.9767	pathogenic	-0.869	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	N

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.