TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6416	19471;19472;19473	chr2:178728680;178728679;178728678	chr2:179593407;179593406;179593405
N2AB	6099	18520;18521;18522	chr2:178728680;178728679;178728678	chr2:179593407;179593406;179593405
N2A	5172	15739;15740;15741	chr2:178728680;178728679;178728678	chr2:179593407;179593406;179593405
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: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-48
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.1971
• 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/G	rs1431823102	-2.376	0.971	D	0.859	0.772	0.933126727598	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	1.18203E-03	None	0	0	None	0	None	0	0	0
V/G	rs1431823102	-2.376	0.971	D	0.859	0.772	0.933126727598	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
V/G	rs1431823102	-2.376	0.971	D	0.859	0.772	0.933126727598	gnomAD-4.0.0	6.57333E-06	None	None	None	None	N	None	0	6.55136E-05	None	0	0	None	0	0	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	0.4936	ambiguous	0.4769	ambiguous	-1.695	Destabilizing	0.698	D	0.665	neutral	D	0.550197668	None	None	N
V/C	0.8914	likely_pathogenic	0.8887	pathogenic	-0.983	Destabilizing	0.998	D	0.73	prob.delet.	None	None	None	None	N
V/D	0.9362	likely_pathogenic	0.9242	pathogenic	-2.15	Highly Destabilizing	0.993	D	0.864	deleterious	None	None	None	None	N
V/E	0.8476	likely_pathogenic	0.8174	pathogenic	-1.937	Destabilizing	0.971	D	0.857	deleterious	D	0.619670235	None	None	N
V/F	0.4505	ambiguous	0.3783	ambiguous	-1.048	Destabilizing	0.956	D	0.775	deleterious	None	None	None	None	N
V/G	0.5759	likely_pathogenic	0.5686	pathogenic	-2.167	Highly Destabilizing	0.971	D	0.859	deleterious	D	0.594132123	None	None	N
V/H	0.9503	likely_pathogenic	0.9371	pathogenic	-1.694	Destabilizing	0.998	D	0.84	deleterious	None	None	None	None	N
V/I	0.108	likely_benign	0.0863	benign	-0.385	Destabilizing	0.019	N	0.274	neutral	None	None	None	None	N
V/K	0.8867	likely_pathogenic	0.8561	pathogenic	-1.274	Destabilizing	0.956	D	0.857	deleterious	None	None	None	None	N
V/L	0.4056	ambiguous	0.2882	benign	-0.385	Destabilizing	0.247	N	0.48	neutral	D	0.537414304	None	None	N
V/M	0.3507	ambiguous	0.26	benign	-0.371	Destabilizing	0.247	N	0.527	neutral	D	0.577709154	None	None	N
V/N	0.8685	likely_pathogenic	0.8352	pathogenic	-1.603	Destabilizing	0.978	D	0.861	deleterious	None	None	None	None	N
V/P	0.7348	likely_pathogenic	0.7517	pathogenic	-0.797	Destabilizing	0.993	D	0.859	deleterious	None	None	None	None	N
V/Q	0.8494	likely_pathogenic	0.8051	pathogenic	-1.474	Destabilizing	0.978	D	0.852	deleterious	None	None	None	None	N
V/R	0.8659	likely_pathogenic	0.8336	pathogenic	-1.155	Destabilizing	0.956	D	0.855	deleterious	None	None	None	None	N
V/S	0.7308	likely_pathogenic	0.7091	pathogenic	-2.164	Highly Destabilizing	0.956	D	0.835	deleterious	None	None	None	None	N
V/T	0.5501	ambiguous	0.5023	ambiguous	-1.809	Destabilizing	0.86	D	0.71	prob.delet.	None	None	None	None	N
V/W	0.9404	likely_pathogenic	0.9341	pathogenic	-1.452	Destabilizing	0.998	D	0.841	deleterious	None	None	None	None	N
V/Y	0.843	likely_pathogenic	0.822	pathogenic	-1.026	Destabilizing	0.978	D	0.756	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.