TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26125	78598;78599;78600	chr2:178567759;178567758;178567757	chr2:179432486;179432485;179432484
N2AB	24484	73675;73676;73677	chr2:178567759;178567758;178567757	chr2:179432486;179432485;179432484
N2A	23557	70894;70895;70896	chr2:178567759;178567758;178567757	chr2:179432486;179432485;179432484
N2B	17060	51403;51404;51405	chr2:178567759;178567758;178567757	chr2:179432486;179432485;179432484
Novex-1	17185	51778;51779;51780	chr2:178567759;178567758;178567757	chr2:179432486;179432485;179432484
Novex-2	17252	51979;51980;51981	chr2:178567759;178567758;178567757	chr2:179432486;179432485;179432484
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: Fn3-78
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.1027
• 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	rs1213696680	None	0.004	N	0.297	0.088	0.386721274199	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.82E-05	0	0	0	0	None	0	0	0	0	0
V/I	rs1213696680	None	0.004	N	0.297	0.088	0.386721274199	gnomAD-4.0.0	1.31492E-05	None	None	None	None	N	None	4.82486E-05	0	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	0.9279	likely_pathogenic	0.9011	pathogenic	-2.212	Highly Destabilizing	0.581	D	0.641	neutral	D	0.532754301	None	None	N
V/C	0.9882	likely_pathogenic	0.9872	pathogenic	-1.377	Destabilizing	0.993	D	0.827	deleterious	None	None	None	None	N
V/D	0.9996	likely_pathogenic	0.9995	pathogenic	-3.137	Highly Destabilizing	0.929	D	0.891	deleterious	None	None	None	None	N
V/E	0.998	likely_pathogenic	0.9973	pathogenic	-2.793	Highly Destabilizing	0.908	D	0.881	deleterious	D	0.560012815	None	None	N
V/F	0.9668	likely_pathogenic	0.9575	pathogenic	-1.252	Destabilizing	0.866	D	0.843	deleterious	None	None	None	None	N
V/G	0.9876	likely_pathogenic	0.9832	pathogenic	-2.84	Highly Destabilizing	0.908	D	0.885	deleterious	D	0.560012815	None	None	N
V/H	0.9996	likely_pathogenic	0.9994	pathogenic	-2.829	Highly Destabilizing	0.993	D	0.881	deleterious	None	None	None	None	N
V/I	0.0898	likely_benign	0.0878	benign	-0.367	Destabilizing	0.004	N	0.297	neutral	N	0.440794383	None	None	N
V/K	0.9984	likely_pathogenic	0.998	pathogenic	-1.721	Destabilizing	0.929	D	0.881	deleterious	None	None	None	None	N
V/L	0.6996	likely_pathogenic	0.6758	pathogenic	-0.367	Destabilizing	0.09	N	0.609	neutral	D	0.526570715	None	None	N
V/M	0.8569	likely_pathogenic	0.8308	pathogenic	-0.575	Destabilizing	0.866	D	0.781	deleterious	None	None	None	None	N
V/N	0.9987	likely_pathogenic	0.9983	pathogenic	-2.514	Highly Destabilizing	0.976	D	0.89	deleterious	None	None	None	None	N
V/P	0.9942	likely_pathogenic	0.9933	pathogenic	-0.966	Destabilizing	0.976	D	0.887	deleterious	None	None	None	None	N
V/Q	0.998	likely_pathogenic	0.9975	pathogenic	-2.07	Highly Destabilizing	0.976	D	0.9	deleterious	None	None	None	None	N
V/R	0.9965	likely_pathogenic	0.9959	pathogenic	-2.016	Highly Destabilizing	0.929	D	0.895	deleterious	None	None	None	None	N
V/S	0.9906	likely_pathogenic	0.9878	pathogenic	-2.961	Highly Destabilizing	0.929	D	0.885	deleterious	None	None	None	None	N
V/T	0.9295	likely_pathogenic	0.9088	pathogenic	-2.445	Highly Destabilizing	0.648	D	0.711	prob.delet.	None	None	None	None	N
V/W	0.9995	likely_pathogenic	0.9994	pathogenic	-1.774	Destabilizing	0.993	D	0.865	deleterious	None	None	None	None	N
V/Y	0.9985	likely_pathogenic	0.9979	pathogenic	-1.464	Destabilizing	0.929	D	0.851	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.