TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18541	55846;55847;55848	chr2:178601376;178601375;178601374	chr2:179466103;179466102;179466101
N2AB	16900	50923;50924;50925	chr2:178601376;178601375;178601374	chr2:179466103;179466102;179466101
N2A	15973	48142;48143;48144	chr2:178601376;178601375;178601374	chr2:179466103;179466102;179466101
N2B	9476	28651;28652;28653	chr2:178601376;178601375;178601374	chr2:179466103;179466102;179466101
Novex-1	9601	29026;29027;29028	chr2:178601376;178601375;178601374	chr2:179466103;179466102;179466101
Novex-2	9668	29227;29228;29229	chr2:178601376;178601375;178601374	chr2:179466103;179466102;179466101
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-22
• Domain position: 63
• Structural Position: 94
• Q(SASA): 0.3487
• 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/A	rs749140088	None	0.984	N	0.597	0.31	0.349870743963	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
P/A	0.1385	likely_benign	0.163	benign	-1.037	Destabilizing	0.984	D	0.597	neutral	N	0.455584903	None	None	N
P/C	0.6702	likely_pathogenic	0.7498	pathogenic	-0.923	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
P/D	0.5946	likely_pathogenic	0.6611	pathogenic	-0.402	Destabilizing	0.998	D	0.745	deleterious	None	None	None	None	N
P/E	0.4101	ambiguous	0.4675	ambiguous	-0.41	Destabilizing	0.998	D	0.743	deleterious	None	None	None	None	N
P/F	0.7894	likely_pathogenic	0.8351	pathogenic	-0.744	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
P/G	0.3263	likely_benign	0.3955	ambiguous	-1.315	Destabilizing	0.994	D	0.709	prob.delet.	None	None	None	None	N
P/H	0.3289	likely_benign	0.3768	ambiguous	-0.641	Destabilizing	1.0	D	0.833	deleterious	N	0.476402893	None	None	N
P/I	0.641	likely_pathogenic	0.7121	pathogenic	-0.395	Destabilizing	0.999	D	0.874	deleterious	None	None	None	None	N
P/K	0.3858	ambiguous	0.4629	ambiguous	-0.822	Destabilizing	0.998	D	0.733	prob.delet.	None	None	None	None	N
P/L	0.2583	likely_benign	0.3001	benign	-0.395	Destabilizing	0.999	D	0.826	deleterious	N	0.463820385	None	None	N
P/M	0.5048	ambiguous	0.582	pathogenic	-0.508	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
P/N	0.4032	ambiguous	0.4666	ambiguous	-0.704	Destabilizing	0.998	D	0.842	deleterious	None	None	None	None	N
P/Q	0.2439	likely_benign	0.2871	benign	-0.814	Destabilizing	0.999	D	0.845	deleterious	None	None	None	None	N
P/R	0.2995	likely_benign	0.344	ambiguous	-0.351	Destabilizing	0.999	D	0.864	deleterious	N	0.453005958	None	None	N
P/S	0.1722	likely_benign	0.2059	benign	-1.259	Destabilizing	0.916	D	0.303	neutral	N	0.408695034	None	None	N
P/T	0.1546	likely_benign	0.1867	benign	-1.14	Destabilizing	0.995	D	0.742	deleterious	N	0.389069123	None	None	N
P/V	0.4313	ambiguous	0.5073	ambiguous	-0.573	Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
P/W	0.8302	likely_pathogenic	0.8731	pathogenic	-0.862	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
P/Y	0.7025	likely_pathogenic	0.7672	pathogenic	-0.572	Destabilizing	1.0	D	0.859	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.