TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33346	100261;100262;100263	chr2:178537073;178537072;178537071	chr2:179401800;179401799;179401798
N2AB	31705	95338;95339;95340	chr2:178537073;178537072;178537071	chr2:179401800;179401799;179401798
N2A	30778	92557;92558;92559	chr2:178537073;178537072;178537071	chr2:179401800;179401799;179401798
N2B	24281	73066;73067;73068	chr2:178537073;178537072;178537071	chr2:179401800;179401799;179401798
Novex-1	24406	73441;73442;73443	chr2:178537073;178537072;178537071	chr2:179401800;179401799;179401798
Novex-2	24473	73642;73643;73644	chr2:178537073;178537072;178537071	chr2:179401800;179401799;179401798
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-130
• Domain position: 57
• Structural Position: 77
• Q(SASA): 0.2349
• 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/F	rs1436237460	-1.444	0.949	N	0.559	0.254	0.386071988338	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
I/F	rs1436237460	-1.444	0.949	N	0.559	0.254	0.386071988338	gnomAD-4.0.0	1.59283E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86017E-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	0.7573	likely_pathogenic	0.7603	pathogenic	-2.038	Highly Destabilizing	0.415	N	0.521	neutral	None	None	None	None	N
I/C	0.9035	likely_pathogenic	0.892	pathogenic	-1.509	Destabilizing	0.996	D	0.607	neutral	None	None	None	None	N
I/D	0.9845	likely_pathogenic	0.9863	pathogenic	-1.442	Destabilizing	0.923	D	0.712	prob.delet.	None	None	None	None	N
I/E	0.9669	likely_pathogenic	0.9711	pathogenic	-1.294	Destabilizing	0.923	D	0.703	prob.neutral	None	None	None	None	N
I/F	0.7018	likely_pathogenic	0.6701	pathogenic	-1.249	Destabilizing	0.949	D	0.559	neutral	N	0.502818703	None	None	N
I/G	0.9717	likely_pathogenic	0.9705	pathogenic	-2.506	Highly Destabilizing	0.923	D	0.673	neutral	None	None	None	None	N
I/H	0.9698	likely_pathogenic	0.9703	pathogenic	-1.809	Destabilizing	0.996	D	0.728	prob.delet.	None	None	None	None	N
I/K	0.9538	likely_pathogenic	0.9499	pathogenic	-1.267	Destabilizing	0.923	D	0.711	prob.delet.	None	None	None	None	N
I/L	0.3383	likely_benign	0.3098	benign	-0.745	Destabilizing	0.19	N	0.326	neutral	N	0.452312525	None	None	N
I/M	0.3504	ambiguous	0.3323	benign	-0.798	Destabilizing	0.949	D	0.536	neutral	N	0.465835376	None	None	N
I/N	0.8383	likely_pathogenic	0.8312	pathogenic	-1.366	Destabilizing	0.901	D	0.736	prob.delet.	N	0.491484202	None	None	N
I/P	0.9663	likely_pathogenic	0.9666	pathogenic	-1.15	Destabilizing	0.961	D	0.731	prob.delet.	None	None	None	None	N
I/Q	0.9384	likely_pathogenic	0.9417	pathogenic	-1.335	Destabilizing	0.961	D	0.739	prob.delet.	None	None	None	None	N
I/R	0.9353	likely_pathogenic	0.9332	pathogenic	-0.965	Destabilizing	0.923	D	0.737	prob.delet.	None	None	None	None	N
I/S	0.7907	likely_pathogenic	0.8082	pathogenic	-2.173	Highly Destabilizing	0.565	D	0.613	neutral	N	0.430435743	None	None	N
I/T	0.7345	likely_pathogenic	0.7373	pathogenic	-1.882	Destabilizing	0.008	N	0.303	neutral	N	0.461625441	None	None	N
I/V	0.1047	likely_benign	0.1012	benign	-1.15	Destabilizing	0.014	N	0.141	neutral	N	0.391226781	None	None	N
I/W	0.9916	likely_pathogenic	0.9908	pathogenic	-1.441	Destabilizing	0.996	D	0.754	deleterious	None	None	None	None	N
I/Y	0.9552	likely_pathogenic	0.9536	pathogenic	-1.149	Destabilizing	0.987	D	0.641	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.