TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7710	23353;23354;23355	chr2:178720634;178720633;178720632	chr2:179585361;179585360;179585359
N2AB	7393	22402;22403;22404	chr2:178720634;178720633;178720632	chr2:179585361;179585360;179585359
N2A	6466	19621;19622;19623	chr2:178720634;178720633;178720632	chr2:179585361;179585360;179585359
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-62
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.5215
• 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	None	None	0.973	N	0.674	0.278	0.438913950225	gnomAD-4.0.0	6.88837E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.02635E-07	0	0
P/S	rs1157011296	None	0.082	N	0.279	0.088	0.0954503805726	gnomAD-4.0.0	1.37752E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80514E-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	0.0619	likely_benign	0.0621	benign	-0.364	Destabilizing	0.295	N	0.405	neutral	N	0.460616412	None	None	N
P/C	0.3901	ambiguous	0.4256	ambiguous	-0.629	Destabilizing	0.989	D	0.673	neutral	None	None	None	None	N
P/D	0.3023	likely_benign	0.3125	benign	-0.1	Destabilizing	0.001	N	0.301	neutral	None	None	None	None	N
P/E	0.2076	likely_benign	0.2134	benign	-0.215	Destabilizing	0.176	N	0.501	neutral	None	None	None	None	N
P/F	0.3014	likely_benign	0.3219	benign	-0.6	Destabilizing	0.997	D	0.675	prob.neutral	None	None	None	None	N
P/G	0.2609	likely_benign	0.2711	benign	-0.481	Destabilizing	0.579	D	0.495	neutral	None	None	None	None	N
P/H	0.1526	likely_benign	0.161	benign	-0.062	Destabilizing	0.993	D	0.585	neutral	None	None	None	None	N
P/I	0.1951	likely_benign	0.1973	benign	-0.21	Destabilizing	0.99	D	0.701	prob.neutral	None	None	None	None	N
P/K	0.2945	likely_benign	0.3104	benign	-0.337	Destabilizing	0.96	D	0.582	neutral	None	None	None	None	N
P/L	0.0907	likely_benign	0.0931	benign	-0.21	Destabilizing	0.973	D	0.674	neutral	N	0.454780288	None	None	N
P/M	0.2142	likely_benign	0.2203	benign	-0.347	Destabilizing	0.998	D	0.59	neutral	None	None	None	None	N
P/N	0.2337	likely_benign	0.2385	benign	-0.093	Destabilizing	0.748	D	0.597	neutral	None	None	None	None	N
P/Q	0.1301	likely_benign	0.1355	benign	-0.319	Destabilizing	0.931	D	0.612	neutral	N	0.457173371	None	None	N
P/R	0.1801	likely_benign	0.1901	benign	0.137	Stabilizing	0.973	D	0.627	neutral	N	0.454780288	None	None	N
P/S	0.0873	likely_benign	0.0894	benign	-0.462	Destabilizing	0.082	N	0.279	neutral	N	0.447028843	None	None	N
P/T	0.0797	likely_benign	0.0797	benign	-0.475	Destabilizing	0.39	N	0.546	neutral	N	0.502826198	None	None	N
P/V	0.1349	likely_benign	0.1377	benign	-0.227	Destabilizing	0.893	D	0.625	neutral	None	None	None	None	N
P/W	0.5176	ambiguous	0.5472	ambiguous	-0.677	Destabilizing	0.999	D	0.652	neutral	None	None	None	None	N
P/Y	0.3299	likely_benign	0.351	ambiguous	-0.374	Destabilizing	0.999	D	0.677	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.