TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28389	85390;85391;85392	chr2:178560967;178560966;178560965	chr2:179425694;179425693;179425692
N2AB	26748	80467;80468;80469	chr2:178560967;178560966;178560965	chr2:179425694;179425693;179425692
N2A	25821	77686;77687;77688	chr2:178560967;178560966;178560965	chr2:179425694;179425693;179425692
N2B	19324	58195;58196;58197	chr2:178560967;178560966;178560965	chr2:179425694;179425693;179425692
Novex-1	19449	58570;58571;58572	chr2:178560967;178560966;178560965	chr2:179425694;179425693;179425692
Novex-2	19516	58771;58772;58773	chr2:178560967;178560966;178560965	chr2:179425694;179425693;179425692
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-143
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.2178
• Predicted PPI site: I

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/T	rs755134776	-2.271	0.062	N	0.641	0.515	0.693152146671	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	0	1.66113E-04
I/T	rs755134776	-2.271	0.062	N	0.641	0.515	0.693152146671	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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
I/A	0.3543	ambiguous	0.3554	ambiguous	-1.934	Destabilizing	None	N	0.415	neutral	None	None	None	None	I
I/C	0.6893	likely_pathogenic	0.6718	pathogenic	-1.269	Destabilizing	0.824	D	0.717	prob.delet.	None	None	None	None	I
I/D	0.9076	likely_pathogenic	0.9009	pathogenic	-1.275	Destabilizing	0.555	D	0.784	deleterious	None	None	None	None	I
I/E	0.821	likely_pathogenic	0.8065	pathogenic	-1.145	Destabilizing	0.38	N	0.768	deleterious	None	None	None	None	I
I/F	0.2838	likely_benign	0.259	benign	-1.112	Destabilizing	0.317	N	0.633	neutral	N	0.521076189	None	None	I
I/G	0.7602	likely_pathogenic	0.7491	pathogenic	-2.39	Highly Destabilizing	0.081	N	0.755	deleterious	None	None	None	None	I
I/H	0.7661	likely_pathogenic	0.7534	pathogenic	-1.605	Destabilizing	0.935	D	0.792	deleterious	None	None	None	None	I
I/K	0.6044	likely_pathogenic	0.5878	pathogenic	-1.348	Destabilizing	0.38	N	0.767	deleterious	None	None	None	None	I
I/L	0.1572	likely_benign	0.1403	benign	-0.688	Destabilizing	None	N	0.224	neutral	N	0.506553105	None	None	I
I/M	0.1568	likely_benign	0.1494	benign	-0.624	Destabilizing	0.317	N	0.597	neutral	D	0.522090147	None	None	I
I/N	0.4905	ambiguous	0.5038	ambiguous	-1.392	Destabilizing	0.484	N	0.795	deleterious	D	0.549095172	None	None	I
I/P	0.7593	likely_pathogenic	0.7391	pathogenic	-1.076	Destabilizing	0.555	D	0.791	deleterious	None	None	None	None	I
I/Q	0.6773	likely_pathogenic	0.6535	pathogenic	-1.361	Destabilizing	0.555	D	0.799	deleterious	None	None	None	None	I
I/R	0.5219	ambiguous	0.5122	ambiguous	-0.985	Destabilizing	0.555	D	0.795	deleterious	None	None	None	None	I
I/S	0.3759	ambiguous	0.3897	ambiguous	-2.146	Highly Destabilizing	0.062	N	0.732	prob.delet.	D	0.525964488	None	None	I
I/T	0.2835	likely_benign	0.2833	benign	-1.87	Destabilizing	0.062	N	0.641	neutral	N	0.507771327	None	None	I
I/V	0.0781	likely_benign	0.0737	benign	-1.076	Destabilizing	None	N	0.183	neutral	N	0.445296126	None	None	I
I/W	0.9338	likely_pathogenic	0.9174	pathogenic	-1.298	Destabilizing	0.935	D	0.794	deleterious	None	None	None	None	I
I/Y	0.6856	likely_pathogenic	0.6818	pathogenic	-1.029	Destabilizing	0.555	D	0.731	prob.delet.	None	None	None	None	I

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.