TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21055	63388;63389;63390	chr2:178588562;178588561;178588560	chr2:179453289;179453288;179453287
N2AB	19414	58465;58466;58467	chr2:178588562;178588561;178588560	chr2:179453289;179453288;179453287
N2A	18487	55684;55685;55686	chr2:178588562;178588561;178588560	chr2:179453289;179453288;179453287
N2B	11990	36193;36194;36195	chr2:178588562;178588561;178588560	chr2:179453289;179453288;179453287
Novex-1	12115	36568;36569;36570	chr2:178588562;178588561;178588560	chr2:179453289;179453288;179453287
Novex-2	12182	36769;36770;36771	chr2:178588562;178588561;178588560	chr2:179453289;179453288;179453287
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCG
• RefSeq wild type template codon: GGC
• Domain: Fn3-40
• Domain position: 93
• Structural Position: 126
• Q(SASA): 0.4189
• 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
P/L	rs779343098	-0.075	0.995	N	0.75	0.367	0.383089235449	gnomAD-2.1.1	1.08E-05	None	None	None	None	N	None	0	0	None	0	6.28E-05	None	0	None	0	1.12E-05	0
P/L	rs779343098	-0.075	0.995	N	0.75	0.367	0.383089235449	gnomAD-4.0.0	7.32158E-06	None	None	None	None	N	None	0	0	None	0	2.82167E-05	None	0	0	6.38672E-06	0	3.39328E-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
P/A	0.0835	likely_benign	0.075	benign	-0.987	Destabilizing	0.841	D	0.672	prob.neutral	N	0.487806391	None	None	N
P/C	0.4854	ambiguous	0.4291	ambiguous	-0.679	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
P/D	0.6756	likely_pathogenic	0.5808	pathogenic	-0.927	Destabilizing	0.98	D	0.681	prob.neutral	None	None	None	None	N
P/E	0.4962	ambiguous	0.4174	ambiguous	-1.012	Destabilizing	0.98	D	0.689	prob.delet.	None	None	None	None	N
P/F	0.4765	ambiguous	0.3946	ambiguous	-0.972	Destabilizing	0.997	D	0.853	deleterious	None	None	None	None	N
P/G	0.3759	ambiguous	0.2982	benign	-1.195	Destabilizing	0.875	D	0.757	deleterious	None	None	None	None	N
P/H	0.325	likely_benign	0.2746	benign	-0.727	Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
P/I	0.3847	ambiguous	0.3117	benign	-0.558	Destabilizing	0.99	D	0.853	deleterious	None	None	None	None	N
P/K	0.6123	likely_pathogenic	0.5378	ambiguous	-0.93	Destabilizing	0.98	D	0.665	prob.neutral	None	None	None	None	N
P/L	0.167	likely_benign	0.134	benign	-0.558	Destabilizing	0.995	D	0.75	deleterious	N	0.506218794	None	None	N
P/M	0.3376	likely_benign	0.2739	benign	-0.404	Destabilizing	0.999	D	0.821	deleterious	None	None	None	None	N
P/N	0.4654	ambiguous	0.3788	ambiguous	-0.596	Destabilizing	0.98	D	0.799	deleterious	None	None	None	None	N
P/Q	0.3361	likely_benign	0.2756	benign	-0.865	Destabilizing	0.989	D	0.781	deleterious	N	0.491569272	None	None	N
P/R	0.4601	ambiguous	0.3744	ambiguous	-0.303	Destabilizing	0.989	D	0.833	deleterious	N	0.471819176	None	None	N
P/S	0.17	likely_benign	0.1416	benign	-0.976	Destabilizing	0.247	N	0.391	neutral	N	0.51002989	None	None	N
P/T	0.1547	likely_benign	0.1297	benign	-0.966	Destabilizing	0.949	D	0.757	deleterious	N	0.515417067	None	None	N
P/V	0.2504	likely_benign	0.2005	benign	-0.665	Destabilizing	0.98	D	0.756	deleterious	None	None	None	None	N
P/W	0.6749	likely_pathogenic	0.5927	pathogenic	-1.071	Destabilizing	0.999	D	0.814	deleterious	None	None	None	None	N
P/Y	0.4717	ambiguous	0.394	ambiguous	-0.809	Destabilizing	0.999	D	0.851	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.