TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28725	86398;86399;86400	chr2:178559959;178559958;178559957	chr2:179424686;179424685;179424684
N2AB	27084	81475;81476;81477	chr2:178559959;178559958;178559957	chr2:179424686;179424685;179424684
N2A	26157	78694;78695;78696	chr2:178559959;178559958;178559957	chr2:179424686;179424685;179424684
N2B	19660	59203;59204;59205	chr2:178559959;178559958;178559957	chr2:179424686;179424685;179424684
Novex-1	19785	59578;59579;59580	chr2:178559959;178559958;178559957	chr2:179424686;179424685;179424684
Novex-2	19852	59779;59780;59781	chr2:178559959;178559958;178559957	chr2:179424686;179424685;179424684
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: Fn3-97
• Domain position: 75
• Structural Position: 108
• Q(SASA): 0.1165
• 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	None	None	0.014	N	0.237	0.172	0.581056753333	gnomAD-4.0.0	1.59134E-06	None	None	None	None	N	None	5.65355E-05	0	None	0	0	None	0	0	0	0	0
V/L	rs1216305497	-0.629	0.247	N	0.527	0.524	0.565281569661	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
V/L	rs1216305497	-0.629	0.247	N	0.527	0.524	0.565281569661	gnomAD-4.0.0	1.59134E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43279E-05	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	0.9184	likely_pathogenic	0.8918	pathogenic	-2.597	Highly Destabilizing	0.822	D	0.619	neutral	D	0.531906424	None	None	N
V/C	0.967	likely_pathogenic	0.9543	pathogenic	-2.245	Highly Destabilizing	0.998	D	0.717	prob.delet.	None	None	None	None	N
V/D	0.9988	likely_pathogenic	0.9977	pathogenic	-3.467	Highly Destabilizing	0.993	D	0.857	deleterious	None	None	None	None	N
V/E	0.9951	likely_pathogenic	0.9914	pathogenic	-3.173	Highly Destabilizing	0.99	D	0.817	deleterious	D	0.632501806	None	None	N
V/F	0.8981	likely_pathogenic	0.8668	pathogenic	-1.294	Destabilizing	0.956	D	0.727	prob.delet.	None	None	None	None	N
V/G	0.9498	likely_pathogenic	0.9342	pathogenic	-3.164	Highly Destabilizing	0.971	D	0.847	deleterious	D	0.632501806	None	None	N
V/H	0.9985	likely_pathogenic	0.9974	pathogenic	-2.874	Highly Destabilizing	0.998	D	0.815	deleterious	None	None	None	None	N
V/I	0.0913	likely_benign	0.0866	benign	-0.942	Destabilizing	0.014	N	0.237	neutral	N	0.519383745	None	None	N
V/K	0.9961	likely_pathogenic	0.9934	pathogenic	-2.019	Highly Destabilizing	0.978	D	0.821	deleterious	None	None	None	None	N
V/L	0.7306	likely_pathogenic	0.5697	pathogenic	-0.942	Destabilizing	0.247	N	0.527	neutral	N	0.512708851	None	None	N
V/M	0.7827	likely_pathogenic	0.6911	pathogenic	-1.372	Destabilizing	0.956	D	0.671	neutral	None	None	None	None	N
V/N	0.9938	likely_pathogenic	0.9896	pathogenic	-2.633	Highly Destabilizing	0.993	D	0.859	deleterious	None	None	None	None	N
V/P	0.9963	likely_pathogenic	0.9952	pathogenic	-1.477	Destabilizing	0.993	D	0.833	deleterious	None	None	None	None	N
V/Q	0.9933	likely_pathogenic	0.9893	pathogenic	-2.309	Highly Destabilizing	0.993	D	0.84	deleterious	None	None	None	None	N
V/R	0.9918	likely_pathogenic	0.9878	pathogenic	-2.017	Highly Destabilizing	0.993	D	0.865	deleterious	None	None	None	None	N
V/S	0.9775	likely_pathogenic	0.9689	pathogenic	-3.151	Highly Destabilizing	0.978	D	0.82	deleterious	None	None	None	None	N
V/T	0.9399	likely_pathogenic	0.9181	pathogenic	-2.713	Highly Destabilizing	0.86	D	0.671	neutral	None	None	None	None	N
V/W	0.9981	likely_pathogenic	0.997	pathogenic	-1.831	Destabilizing	0.998	D	0.78	deleterious	None	None	None	None	N
V/Y	0.9923	likely_pathogenic	0.9871	pathogenic	-1.619	Destabilizing	0.978	D	0.738	prob.delet.	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.