TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4800	14623;14624;14625	chr2:178736048;178736047;178736046	chr2:179600775;179600774;179600773
N2AB	4483	13672;13673;13674	chr2:178736048;178736047;178736046	chr2:179600775;179600774;179600773
N2A	3556	10891;10892;10893	chr2:178736048;178736047;178736046	chr2:179600775;179600774;179600773
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: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-31
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.6373
• 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
R/S	rs751522505	-0.046	0.826	N	0.477	0.342	0.278968121808	gnomAD-2.1.1	4.23E-06	None	None	None	None	N	None	0	0	None	0	5.67E-05	None	0	None	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
R/A	0.5957	likely_pathogenic	0.7205	pathogenic	-0.77	Destabilizing	0.863	D	0.477	neutral	None	None	None	None	N
R/C	0.2177	likely_benign	0.3688	ambiguous	-0.681	Destabilizing	0.999	D	0.487	neutral	None	None	None	None	N
R/D	0.9013	likely_pathogenic	0.9479	pathogenic	0.057	Stabilizing	0.884	D	0.531	neutral	None	None	None	None	N
R/E	0.5578	ambiguous	0.6725	pathogenic	0.181	Stabilizing	0.863	D	0.449	neutral	None	None	None	None	N
R/F	0.6976	likely_pathogenic	0.8063	pathogenic	-0.667	Destabilizing	0.997	D	0.488	neutral	None	None	None	None	N
R/G	0.4567	ambiguous	0.6165	pathogenic	-1.066	Destabilizing	0.92	D	0.521	neutral	N	0.485538884	None	None	N
R/H	0.148	likely_benign	0.2012	benign	-1.461	Destabilizing	0.991	D	0.503	neutral	None	None	None	None	N
R/I	0.4784	ambiguous	0.6144	pathogenic	0.019	Stabilizing	0.996	D	0.505	neutral	N	0.475839647	None	None	N
R/K	0.1491	likely_benign	0.1513	benign	-0.634	Destabilizing	0.021	N	0.156	neutral	N	0.414667604	None	None	N
R/L	0.3882	ambiguous	0.5138	ambiguous	0.019	Stabilizing	0.969	D	0.543	neutral	None	None	None	None	N
R/M	0.4828	ambiguous	0.5989	pathogenic	-0.339	Destabilizing	0.997	D	0.491	neutral	None	None	None	None	N
R/N	0.8151	likely_pathogenic	0.8877	pathogenic	-0.175	Destabilizing	0.17	N	0.191	neutral	None	None	None	None	N
R/P	0.6089	likely_pathogenic	0.7291	pathogenic	-0.224	Destabilizing	0.997	D	0.499	neutral	None	None	None	None	N
R/Q	0.142	likely_benign	0.1822	benign	-0.322	Destabilizing	0.939	D	0.487	neutral	None	None	None	None	N
R/S	0.6875	likely_pathogenic	0.8057	pathogenic	-0.935	Destabilizing	0.826	D	0.477	neutral	N	0.490136297	None	None	N
R/T	0.5021	ambiguous	0.6344	pathogenic	-0.626	Destabilizing	0.92	D	0.499	neutral	N	0.487512472	None	None	N
R/V	0.5708	likely_pathogenic	0.6847	pathogenic	-0.224	Destabilizing	0.969	D	0.508	neutral	None	None	None	None	N
R/W	0.2497	likely_benign	0.4026	ambiguous	-0.373	Destabilizing	0.999	D	0.55	neutral	None	None	None	None	N
R/Y	0.4858	ambiguous	0.645	pathogenic	-0.07	Destabilizing	0.997	D	0.522	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.