TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23742	71449;71450;71451	chr2:178574908;178574907;178574906	chr2:179439635;179439634;179439633
N2AB	22101	66526;66527;66528	chr2:178574908;178574907;178574906	chr2:179439635;179439634;179439633
N2A	21174	63745;63746;63747	chr2:178574908;178574907;178574906	chr2:179439635;179439634;179439633
N2B	14677	44254;44255;44256	chr2:178574908;178574907;178574906	chr2:179439635;179439634;179439633
Novex-1	14802	44629;44630;44631	chr2:178574908;178574907;178574906	chr2:179439635;179439634;179439633
Novex-2	14869	44830;44831;44832	chr2:178574908;178574907;178574906	chr2:179439635;179439634;179439633
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-60
• Domain position: 17
• Structural Position: 18
• Q(SASA): 0.4538
• 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
D/H	rs1205041822	None	0.998	N	0.758	0.349	0.239305524855	gnomAD-4.0.0	2.05389E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79952E-06	0	1.65782E-05
D/N	rs1205041822	None	0.988	N	0.711	0.243	0.185906805712	gnomAD-4.0.0	6.8463E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9976E-07	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
D/A	0.3596	ambiguous	0.423	ambiguous	-1.083	Destabilizing	0.958	D	0.717	prob.delet.	D	0.522868688	None	None	N
D/C	0.7798	likely_pathogenic	0.8299	pathogenic	-0.363	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
D/E	0.2197	likely_benign	0.2445	benign	-0.677	Destabilizing	0.067	N	0.21	neutral	N	0.488140039	None	None	N
D/F	0.8285	likely_pathogenic	0.8658	pathogenic	-0.927	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
D/G	0.3723	ambiguous	0.4273	ambiguous	-1.368	Destabilizing	0.958	D	0.707	prob.neutral	N	0.502858775	None	None	N
D/H	0.5238	ambiguous	0.5954	pathogenic	-1.125	Destabilizing	0.998	D	0.758	deleterious	N	0.47546153	None	None	N
D/I	0.6544	likely_pathogenic	0.726	pathogenic	-0.331	Destabilizing	0.995	D	0.827	deleterious	None	None	None	None	N
D/K	0.6804	likely_pathogenic	0.745	pathogenic	-0.357	Destabilizing	0.982	D	0.747	deleterious	None	None	None	None	N
D/L	0.6168	likely_pathogenic	0.7094	pathogenic	-0.331	Destabilizing	0.991	D	0.82	deleterious	None	None	None	None	N
D/M	0.76	likely_pathogenic	0.8243	pathogenic	0.249	Stabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
D/N	0.1154	likely_benign	0.1443	benign	-0.724	Destabilizing	0.988	D	0.711	prob.delet.	N	0.476632179	None	None	N
D/P	0.9646	likely_pathogenic	0.9663	pathogenic	-0.561	Destabilizing	0.995	D	0.795	deleterious	None	None	None	None	N
D/Q	0.5409	ambiguous	0.6106	pathogenic	-0.677	Destabilizing	0.982	D	0.769	deleterious	None	None	None	None	N
D/R	0.7118	likely_pathogenic	0.7531	pathogenic	-0.27	Destabilizing	0.991	D	0.812	deleterious	None	None	None	None	N
D/S	0.1608	likely_benign	0.2003	benign	-0.991	Destabilizing	0.968	D	0.631	neutral	None	None	None	None	N
D/T	0.2667	likely_benign	0.3497	ambiguous	-0.747	Destabilizing	0.991	D	0.76	deleterious	None	None	None	None	N
D/V	0.4507	ambiguous	0.5285	ambiguous	-0.561	Destabilizing	0.994	D	0.823	deleterious	N	0.479815482	None	None	N
D/W	0.9664	likely_pathogenic	0.9721	pathogenic	-0.681	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
D/Y	0.4505	ambiguous	0.4996	ambiguous	-0.662	Destabilizing	0.999	D	0.823	deleterious	N	0.509022553	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.