TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26322	79189;79190;79191	chr2:178567168;178567167;178567166	chr2:179431895;179431894;179431893
N2AB	24681	74266;74267;74268	chr2:178567168;178567167;178567166	chr2:179431895;179431894;179431893
N2A	23754	71485;71486;71487	chr2:178567168;178567167;178567166	chr2:179431895;179431894;179431893
N2B	17257	51994;51995;51996	chr2:178567168;178567167;178567166	chr2:179431895;179431894;179431893
Novex-1	17382	52369;52370;52371	chr2:178567168;178567167;178567166	chr2:179431895;179431894;179431893
Novex-2	17449	52570;52571;52572	chr2:178567168;178567167;178567166	chr2:179431895;179431894;179431893
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-79
• Domain position: 37
• Structural Position: 38
• Q(SASA): 0.1164
• 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
Y/F	None	None	0.999	D	0.667	0.797	0.716943719587	gnomAD-4.0.0	1.5922E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86025E-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
Y/A	0.9962	likely_pathogenic	0.9956	pathogenic	-3.918	Highly Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
Y/C	0.9009	likely_pathogenic	0.8976	pathogenic	-2.09	Highly Destabilizing	1.0	D	0.861	deleterious	D	0.665335232	None	None	N
Y/D	0.9977	likely_pathogenic	0.9971	pathogenic	-3.743	Highly Destabilizing	1.0	D	0.887	deleterious	D	0.665738841	None	None	N
Y/E	0.9993	likely_pathogenic	0.9992	pathogenic	-3.55	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
Y/F	0.1726	likely_benign	0.1639	benign	-1.713	Destabilizing	0.999	D	0.667	neutral	D	0.557350103	None	None	N
Y/G	0.9919	likely_pathogenic	0.9907	pathogenic	-4.26	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
Y/H	0.9694	likely_pathogenic	0.9653	pathogenic	-2.876	Highly Destabilizing	1.0	D	0.811	deleterious	D	0.649315871	None	None	N
Y/I	0.9712	likely_pathogenic	0.968	pathogenic	-2.73	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
Y/K	0.9987	likely_pathogenic	0.9985	pathogenic	-2.66	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
Y/L	0.9346	likely_pathogenic	0.9353	pathogenic	-2.73	Highly Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
Y/M	0.9823	likely_pathogenic	0.9808	pathogenic	-2.371	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
Y/N	0.9849	likely_pathogenic	0.9821	pathogenic	-3.278	Highly Destabilizing	1.0	D	0.877	deleterious	D	0.665738841	None	None	N
Y/P	0.9995	likely_pathogenic	0.9994	pathogenic	-3.147	Highly Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
Y/Q	0.998	likely_pathogenic	0.9976	pathogenic	-3.072	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
Y/R	0.9934	likely_pathogenic	0.9926	pathogenic	-2.328	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
Y/S	0.9864	likely_pathogenic	0.9836	pathogenic	-3.601	Highly Destabilizing	1.0	D	0.89	deleterious	D	0.665738841	None	None	N
Y/T	0.9946	likely_pathogenic	0.9937	pathogenic	-3.312	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
Y/V	0.9474	likely_pathogenic	0.9438	pathogenic	-3.147	Highly Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
Y/W	0.83	likely_pathogenic	0.8107	pathogenic	-0.872	Destabilizing	1.0	D	0.8	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.