TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4740	14443;14444;14445	chr2:178738235;178738234;178738233	chr2:179602962;179602961;179602960
N2AB	4423	13492;13493;13494	chr2:178738235;178738234;178738233	chr2:179602962;179602961;179602960
N2A	3496	10711;10712;10713	chr2:178738235;178738234;178738233	chr2:179602962;179602961;179602960
N2B	4377	13354;13355;13356	chr2:178738235;178738234;178738233	chr2:179602962;179602961;179602960
Novex-1	4502	13729;13730;13731	chr2:178738235;178738234;178738233	chr2:179602962;179602961;179602960
Novex-2	4569	13930;13931;13932	chr2:178738235;178738234;178738233	chr2:179602962;179602961;179602960
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-30
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.1887
• 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
I/V	rs1381364366	-1.135	0.003	N	0.16	0.267	0.496428787267	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
I/V	rs1381364366	-1.135	0.003	N	0.16	0.267	0.496428787267	gnomAD-4.0.0	1.59171E-06	None	None	None	None	N	None	0	2.28728E-05	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
I/A	0.9406	likely_pathogenic	0.966	pathogenic	-2.02	Highly Destabilizing	0.373	N	0.497	neutral	None	None	None	None	N
I/C	0.973	likely_pathogenic	0.9837	pathogenic	-0.999	Destabilizing	0.996	D	0.571	neutral	None	None	None	None	N
I/D	0.9959	likely_pathogenic	0.9971	pathogenic	-2.262	Highly Destabilizing	0.02	N	0.505	neutral	None	None	None	None	N
I/E	0.9883	likely_pathogenic	0.9917	pathogenic	-2.027	Highly Destabilizing	0.59	D	0.631	neutral	None	None	None	None	N
I/F	0.5722	likely_pathogenic	0.7098	pathogenic	-1.277	Destabilizing	0.884	D	0.576	neutral	D	0.5506534	None	None	N
I/G	0.9885	likely_pathogenic	0.9934	pathogenic	-2.517	Highly Destabilizing	0.953	D	0.621	neutral	None	None	None	None	N
I/H	0.9826	likely_pathogenic	0.9897	pathogenic	-1.924	Destabilizing	0.996	D	0.632	neutral	None	None	None	None	N
I/K	0.9681	likely_pathogenic	0.9786	pathogenic	-1.348	Destabilizing	0.91	D	0.638	neutral	None	None	None	None	N
I/L	0.1972	likely_benign	0.3027	benign	-0.583	Destabilizing	0.003	N	0.169	neutral	N	0.450274191	None	None	N
I/M	0.2816	likely_benign	0.3557	ambiguous	-0.429	Destabilizing	0.164	N	0.387	neutral	D	0.54989227	None	None	N
I/N	0.9411	likely_pathogenic	0.9505	pathogenic	-1.747	Destabilizing	0.884	D	0.661	neutral	D	0.673263123	None	None	N
I/P	0.9938	likely_pathogenic	0.9948	pathogenic	-1.045	Destabilizing	0.984	D	0.666	neutral	None	None	None	None	N
I/Q	0.9776	likely_pathogenic	0.9863	pathogenic	-1.589	Destabilizing	0.953	D	0.673	neutral	None	None	None	None	N
I/R	0.9534	likely_pathogenic	0.9719	pathogenic	-1.213	Destabilizing	0.91	D	0.673	neutral	None	None	None	None	N
I/S	0.964	likely_pathogenic	0.9743	pathogenic	-2.373	Highly Destabilizing	0.684	D	0.55	neutral	D	0.64418821	None	None	N
I/T	0.9313	likely_pathogenic	0.9489	pathogenic	-1.993	Destabilizing	0.684	D	0.507	neutral	D	0.689580296	None	None	N
I/V	0.1943	likely_benign	0.2366	benign	-1.045	Destabilizing	0.003	N	0.16	neutral	N	0.492079699	None	None	N
I/W	0.9783	likely_pathogenic	0.9865	pathogenic	-1.633	Destabilizing	0.996	D	0.671	neutral	None	None	None	None	N
I/Y	0.918	likely_pathogenic	0.9436	pathogenic	-1.258	Destabilizing	0.953	D	0.62	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.