TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33692	101299;101300;101301	chr2:178535541;178535540;178535539	chr2:179400268;179400267;179400266
N2AB	32051	96376;96377;96378	chr2:178535541;178535540;178535539	chr2:179400268;179400267;179400266
N2A	31124	93595;93596;93597	chr2:178535541;178535540;178535539	chr2:179400268;179400267;179400266
N2B	24627	74104;74105;74106	chr2:178535541;178535540;178535539	chr2:179400268;179400267;179400266
Novex-1	24752	74479;74480;74481	chr2:178535541;178535540;178535539	chr2:179400268;179400267;179400266
Novex-2	24819	74680;74681;74682	chr2:178535541;178535540;178535539	chr2:179400268;179400267;179400266
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: Fn3-132
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2479
• 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/R	rs755832382	-0.729	0.973	N	0.867	0.418	0.60087810649	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.65618E-04
P/R	rs755832382	-0.729	0.973	N	0.867	0.418	0.60087810649	gnomAD-4.0.0	1.59118E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41196E-04	0	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	0.1083	likely_benign	0.1256	benign	-1.635	Destabilizing	0.005	N	0.457	neutral	N	0.466124397	None	None	N
P/C	0.7376	likely_pathogenic	0.7245	pathogenic	-1.272	Destabilizing	0.989	D	0.855	deleterious	None	None	None	None	N
P/D	0.9491	likely_pathogenic	0.9458	pathogenic	-2.24	Highly Destabilizing	0.489	N	0.844	deleterious	None	None	None	None	N
P/E	0.7737	likely_pathogenic	0.7381	pathogenic	-2.258	Highly Destabilizing	0.603	D	0.835	deleterious	None	None	None	None	N
P/F	0.8683	likely_pathogenic	0.8575	pathogenic	-1.447	Destabilizing	0.99	D	0.879	deleterious	None	None	None	None	N
P/G	0.6787	likely_pathogenic	0.7035	pathogenic	-1.92	Destabilizing	0.583	D	0.797	deleterious	None	None	None	None	N
P/H	0.6555	likely_pathogenic	0.6304	pathogenic	-1.4	Destabilizing	0.993	D	0.847	deleterious	None	None	None	None	N
P/I	0.7137	likely_pathogenic	0.6581	pathogenic	-0.943	Destabilizing	0.99	D	0.873	deleterious	None	None	None	None	N
P/K	0.8013	likely_pathogenic	0.7177	pathogenic	-1.333	Destabilizing	0.96	D	0.838	deleterious	None	None	None	None	N
P/L	0.4813	ambiguous	0.4577	ambiguous	-0.943	Destabilizing	0.912	D	0.83	deleterious	N	0.514595641	None	None	N
P/M	0.7312	likely_pathogenic	0.7283	pathogenic	-0.71	Destabilizing	0.998	D	0.847	deleterious	None	None	None	None	N
P/N	0.8663	likely_pathogenic	0.8584	pathogenic	-1.242	Destabilizing	0.751	D	0.868	deleterious	None	None	None	None	N
P/Q	0.5292	ambiguous	0.5026	ambiguous	-1.512	Destabilizing	0.932	D	0.819	deleterious	N	0.480068972	None	None	N
P/R	0.6338	likely_pathogenic	0.5282	ambiguous	-0.72	Destabilizing	0.973	D	0.867	deleterious	N	0.486830148	None	None	N
P/S	0.3188	likely_benign	0.3245	benign	-1.661	Destabilizing	0.083	N	0.563	neutral	N	0.475207126	None	None	N
P/T	0.4107	ambiguous	0.3767	ambiguous	-1.583	Destabilizing	0.394	N	0.83	deleterious	N	0.502567773	None	None	N
P/V	0.5551	ambiguous	0.5159	ambiguous	-1.142	Destabilizing	0.708	D	0.839	deleterious	None	None	None	None	N
P/W	0.9615	likely_pathogenic	0.9554	pathogenic	-1.629	Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
P/Y	0.8874	likely_pathogenic	0.8619	pathogenic	-1.338	Destabilizing	0.997	D	0.879	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.