TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2500	7723;7724;7725	chr2:178773558;178773557;178773556	chr2:179638285;179638284;179638283
N2AB	2500	7723;7724;7725	chr2:178773558;178773557;178773556	chr2:179638285;179638284;179638283
N2A	2500	7723;7724;7725	chr2:178773558;178773557;178773556	chr2:179638285;179638284;179638283
N2B	2454	7585;7586;7587	chr2:178773558;178773557;178773556	chr2:179638285;179638284;179638283
Novex-1	2454	7585;7586;7587	chr2:178773558;178773557;178773556	chr2:179638285;179638284;179638283
Novex-2	2454	7585;7586;7587	chr2:178773558;178773557;178773556	chr2:179638285;179638284;179638283
Novex-3	2500	7723;7724;7725	chr2:178773558;178773557;178773556	chr2:179638285;179638284;179638283

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-14
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.1569
• 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
Q/R	rs1417536595	-0.624	0.997	N	0.631	0.416	0.124217242631	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	6.15E-05	0	None	0	0	None	0	None	0	0	0
Q/R	rs1417536595	-0.624	0.997	N	0.631	0.416	0.124217242631	gnomAD-4.0.0	1.59066E-06	None	None	None	None	N	None	5.65355E-05	0	None	0	0	None	0	0	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
Q/A	0.6111	likely_pathogenic	0.6076	pathogenic	-1.075	Destabilizing	0.997	D	0.691	prob.neutral	None	None	None	None	N
Q/C	0.8284	likely_pathogenic	0.8245	pathogenic	-0.775	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
Q/D	0.9731	likely_pathogenic	0.9698	pathogenic	-2.495	Highly Destabilizing	0.997	D	0.625	neutral	None	None	None	None	N
Q/E	0.3316	likely_benign	0.3222	benign	-2.127	Highly Destabilizing	0.992	D	0.587	neutral	D	0.531369096	None	None	N
Q/F	0.9017	likely_pathogenic	0.9018	pathogenic	-0.478	Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
Q/G	0.7846	likely_pathogenic	0.7747	pathogenic	-1.587	Destabilizing	0.997	D	0.723	prob.delet.	None	None	None	None	N
Q/H	0.5191	ambiguous	0.5014	ambiguous	-1.164	Destabilizing	0.999	D	0.751	deleterious	N	0.439419769	None	None	N
Q/I	0.6867	likely_pathogenic	0.6918	pathogenic	0.352	Stabilizing	0.999	D	0.839	deleterious	None	None	None	None	N
Q/K	0.5555	ambiguous	0.5389	ambiguous	-0.567	Destabilizing	0.997	D	0.632	neutral	N	0.491056558	None	None	N
Q/L	0.3474	ambiguous	0.3563	ambiguous	0.352	Stabilizing	0.997	D	0.723	prob.delet.	N	0.43718761	None	None	N
Q/M	0.5569	ambiguous	0.5625	ambiguous	0.412	Stabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
Q/N	0.6976	likely_pathogenic	0.6914	pathogenic	-1.818	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
Q/P	0.9578	likely_pathogenic	0.9591	pathogenic	-0.098	Destabilizing	0.999	D	0.76	deleterious	D	0.531369096	None	None	N
Q/R	0.5524	ambiguous	0.5383	ambiguous	-0.939	Destabilizing	0.997	D	0.631	neutral	N	0.440563572	None	None	N
Q/S	0.6788	likely_pathogenic	0.6659	pathogenic	-1.977	Destabilizing	0.997	D	0.618	neutral	None	None	None	None	N
Q/T	0.6152	likely_pathogenic	0.5931	pathogenic	-1.4	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
Q/V	0.5274	ambiguous	0.5355	ambiguous	-0.098	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
Q/W	0.9257	likely_pathogenic	0.9246	pathogenic	-0.643	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
Q/Y	0.7641	likely_pathogenic	0.7644	pathogenic	-0.188	Destabilizing	0.999	D	0.798	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.