TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20409	61450;61451;61452	chr2:178590500;178590499;178590498	chr2:179455227;179455226;179455225
N2AB	18768	56527;56528;56529	chr2:178590500;178590499;178590498	chr2:179455227;179455226;179455225
N2A	17841	53746;53747;53748	chr2:178590500;178590499;178590498	chr2:179455227;179455226;179455225
N2B	11344	34255;34256;34257	chr2:178590500;178590499;178590498	chr2:179455227;179455226;179455225
Novex-1	11469	34630;34631;34632	chr2:178590500;178590499;178590498	chr2:179455227;179455226;179455225
Novex-2	11536	34831;34832;34833	chr2:178590500;178590499;178590498	chr2:179455227;179455226;179455225
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-36
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.0874
• 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
E/K	rs2049975714	None	0.619	N	0.423	0.405	0.316494231283	gnomAD-4.0.0	2.05339E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69917E-06	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
E/A	0.8515	likely_pathogenic	0.8853	pathogenic	-2.187	Highly Destabilizing	0.992	D	0.693	prob.neutral	N	0.520543443	None	None	N
E/C	0.9769	likely_pathogenic	0.9861	pathogenic	-1.331	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
E/D	0.8431	likely_pathogenic	0.811	pathogenic	-1.912	Destabilizing	0.992	D	0.637	neutral	N	0.48409467	None	None	N
E/F	0.9774	likely_pathogenic	0.9865	pathogenic	-1.838	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
E/G	0.9482	likely_pathogenic	0.9494	pathogenic	-2.553	Highly Destabilizing	0.998	D	0.768	deleterious	D	0.522317869	None	None	N
E/H	0.9694	likely_pathogenic	0.9778	pathogenic	-1.72	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/I	0.9539	likely_pathogenic	0.9663	pathogenic	-1.117	Destabilizing	0.999	D	0.867	deleterious	None	None	None	None	N
E/K	0.9619	likely_pathogenic	0.9661	pathogenic	-2.272	Highly Destabilizing	0.619	D	0.423	neutral	N	0.510882204	None	None	N
E/L	0.9561	likely_pathogenic	0.9685	pathogenic	-1.117	Destabilizing	0.998	D	0.803	deleterious	None	None	None	None	N
E/M	0.9511	likely_pathogenic	0.9662	pathogenic	-0.277	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
E/N	0.9826	likely_pathogenic	0.9834	pathogenic	-2.378	Highly Destabilizing	0.998	D	0.776	deleterious	None	None	None	None	N
E/P	0.9997	likely_pathogenic	0.9996	pathogenic	-1.463	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
E/Q	0.7034	likely_pathogenic	0.7701	pathogenic	-2.096	Highly Destabilizing	0.992	D	0.709	prob.delet.	N	0.51923095	None	None	N
E/R	0.9635	likely_pathogenic	0.9692	pathogenic	-1.963	Destabilizing	0.996	D	0.764	deleterious	None	None	None	None	N
E/S	0.9022	likely_pathogenic	0.9213	pathogenic	-3.074	Highly Destabilizing	0.994	D	0.661	neutral	None	None	None	None	N
E/T	0.9494	likely_pathogenic	0.9613	pathogenic	-2.731	Highly Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
E/V	0.8972	likely_pathogenic	0.9259	pathogenic	-1.463	Destabilizing	0.999	D	0.774	deleterious	N	0.51291012	None	None	N
E/W	0.99	likely_pathogenic	0.9937	pathogenic	-1.886	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
E/Y	0.9593	likely_pathogenic	0.975	pathogenic	-1.712	Destabilizing	1.0	D	0.845	deleterious	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.