TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23962	72109;72110;72111	chr2:178574248;178574247;178574246	chr2:179438975;179438974;179438973
N2AB	22321	67186;67187;67188	chr2:178574248;178574247;178574246	chr2:179438975;179438974;179438973
N2A	21394	64405;64406;64407	chr2:178574248;178574247;178574246	chr2:179438975;179438974;179438973
N2B	14897	44914;44915;44916	chr2:178574248;178574247;178574246	chr2:179438975;179438974;179438973
Novex-1	15022	45289;45290;45291	chr2:178574248;178574247;178574246	chr2:179438975;179438974;179438973
Novex-2	15089	45490;45491;45492	chr2:178574248;178574247;178574246	chr2:179438975;179438974;179438973
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-62
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1247
• 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
E/Q	rs1188261866	-1.858	1.0	N	0.74	0.394	0.28058544554	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
E/Q	rs1188261866	-1.858	1.0	N	0.74	0.394	0.28058544554	gnomAD-4.0.0	1.59284E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86138E-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
E/A	0.9402	likely_pathogenic	0.9572	pathogenic	-1.337	Destabilizing	0.999	D	0.679	prob.neutral	D	0.537331024	None	None	N
E/C	0.9916	likely_pathogenic	0.9933	pathogenic	-0.651	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/D	0.9552	likely_pathogenic	0.9604	pathogenic	-1.772	Destabilizing	0.999	D	0.639	neutral	N	0.500223915	None	None	N
E/F	0.9948	likely_pathogenic	0.9958	pathogenic	-0.987	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
E/G	0.9472	likely_pathogenic	0.962	pathogenic	-1.735	Destabilizing	1.0	D	0.756	deleterious	D	0.545688817	None	None	N
E/H	0.9869	likely_pathogenic	0.9895	pathogenic	-0.93	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
E/I	0.9834	likely_pathogenic	0.9875	pathogenic	-0.196	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
E/K	0.9523	likely_pathogenic	0.963	pathogenic	-1.469	Destabilizing	0.999	D	0.669	neutral	N	0.519934331	None	None	N
E/L	0.9754	likely_pathogenic	0.9819	pathogenic	-0.196	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
E/M	0.9744	likely_pathogenic	0.9803	pathogenic	0.505	Stabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
E/N	0.989	likely_pathogenic	0.9917	pathogenic	-1.742	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
E/P	0.9997	likely_pathogenic	0.9998	pathogenic	-0.562	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
E/Q	0.7339	likely_pathogenic	0.7668	pathogenic	-1.436	Destabilizing	1.0	D	0.74	deleterious	N	0.483712595	None	None	N
E/R	0.9676	likely_pathogenic	0.9747	pathogenic	-1.308	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/S	0.958	likely_pathogenic	0.9676	pathogenic	-2.326	Highly Destabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	N
E/T	0.9779	likely_pathogenic	0.9834	pathogenic	-1.953	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/V	0.9605	likely_pathogenic	0.9699	pathogenic	-0.562	Destabilizing	1.0	D	0.763	deleterious	D	0.526570603	None	None	N
E/W	0.9976	likely_pathogenic	0.9982	pathogenic	-1.097	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
E/Y	0.9902	likely_pathogenic	0.9925	pathogenic	-0.811	Destabilizing	1.0	D	0.788	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.