TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6848	20767;20768;20769	chr2:178725780;178725779;178725778	chr2:179590507;179590506;179590505
N2AB	6531	19816;19817;19818	chr2:178725780;178725779;178725778	chr2:179590507;179590506;179590505
N2A	5604	17035;17036;17037	chr2:178725780;178725779;178725778	chr2:179590507;179590506;179590505
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: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-52
• Domain position: 88
• Structural Position: 174
• Q(SASA): 0.0945
• 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
V/I	rs1413547257	-0.177	0.001	N	0.249	0.098	0.247872288689	gnomAD-4.0.0	1.39113E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.89251E-05	1.77431E-04	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
V/A	0.6621	likely_pathogenic	0.7139	pathogenic	-2.283	Highly Destabilizing	0.296	N	0.642	neutral	D	0.548911813	None	None	N
V/C	0.9258	likely_pathogenic	0.9317	pathogenic	-1.812	Destabilizing	0.991	D	0.805	deleterious	None	None	None	None	N
V/D	0.9873	likely_pathogenic	0.9917	pathogenic	-3.061	Highly Destabilizing	0.906	D	0.863	deleterious	None	None	None	None	N
V/E	0.96	likely_pathogenic	0.9708	pathogenic	-2.766	Highly Destabilizing	0.957	D	0.827	deleterious	D	0.586693931	None	None	N
V/F	0.3795	ambiguous	0.4042	ambiguous	-1.316	Destabilizing	0.826	D	0.799	deleterious	None	None	None	None	N
V/G	0.8394	likely_pathogenic	0.8742	pathogenic	-2.897	Highly Destabilizing	0.879	D	0.83	deleterious	D	0.586693931	None	None	N
V/H	0.9802	likely_pathogenic	0.9821	pathogenic	-2.733	Highly Destabilizing	0.991	D	0.849	deleterious	None	None	None	None	N
V/I	0.068	likely_benign	0.0672	benign	-0.523	Destabilizing	0.001	N	0.249	neutral	N	0.499918123	None	None	N
V/K	0.9652	likely_pathogenic	0.9727	pathogenic	-1.994	Destabilizing	0.906	D	0.821	deleterious	None	None	None	None	N
V/L	0.1768	likely_benign	0.1788	benign	-0.523	Destabilizing	0.001	N	0.273	neutral	N	0.413759711	None	None	N
V/M	0.2291	likely_benign	0.2571	benign	-0.655	Destabilizing	0.826	D	0.711	prob.delet.	None	None	None	None	N
V/N	0.9524	likely_pathogenic	0.9639	pathogenic	-2.549	Highly Destabilizing	0.967	D	0.856	deleterious	None	None	None	None	N
V/P	0.9649	likely_pathogenic	0.9736	pathogenic	-1.086	Destabilizing	0.967	D	0.841	deleterious	None	None	None	None	N
V/Q	0.947	likely_pathogenic	0.9587	pathogenic	-2.246	Highly Destabilizing	0.967	D	0.831	deleterious	None	None	None	None	N
V/R	0.9481	likely_pathogenic	0.9614	pathogenic	-1.983	Destabilizing	0.906	D	0.857	deleterious	None	None	None	None	N
V/S	0.8859	likely_pathogenic	0.9133	pathogenic	-3.16	Highly Destabilizing	0.906	D	0.802	deleterious	None	None	None	None	N
V/T	0.7456	likely_pathogenic	0.7969	pathogenic	-2.7	Highly Destabilizing	0.575	D	0.649	neutral	None	None	None	None	N
V/W	0.9675	likely_pathogenic	0.9711	pathogenic	-1.901	Destabilizing	0.991	D	0.851	deleterious	None	None	None	None	N
V/Y	0.9018	likely_pathogenic	0.9155	pathogenic	-1.511	Destabilizing	0.906	D	0.812	deleterious	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.