TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26163	78712;78713;78714	chr2:178567645;178567644;178567643	chr2:179432372;179432371;179432370
N2AB	24522	73789;73790;73791	chr2:178567645;178567644;178567643	chr2:179432372;179432371;179432370
N2A	23595	71008;71009;71010	chr2:178567645;178567644;178567643	chr2:179432372;179432371;179432370
N2B	17098	51517;51518;51519	chr2:178567645;178567644;178567643	chr2:179432372;179432371;179432370
Novex-1	17223	51892;51893;51894	chr2:178567645;178567644;178567643	chr2:179432372;179432371;179432370
Novex-2	17290	52093;52094;52095	chr2:178567645;178567644;178567643	chr2:179432372;179432371;179432370
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-78
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.0982
• 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/L	rs1428745841	-0.886	0.981	D	0.687	0.521	0.595418376915	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
V/L	rs1428745841	-0.886	0.981	D	0.687	0.521	0.595418376915	gnomAD-4.0.0	1.59481E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86538E-06	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	0.846	likely_pathogenic	0.8656	pathogenic	-2.593	Highly Destabilizing	0.998	D	0.714	prob.delet.	D	0.555771124	None	None	N
V/C	0.9626	likely_pathogenic	0.9625	pathogenic	-1.98	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
V/D	0.999	likely_pathogenic	0.9989	pathogenic	-3.35	Highly Destabilizing	1.0	D	0.906	deleterious	D	0.654325283	None	None	N
V/E	0.9966	likely_pathogenic	0.9963	pathogenic	-3.048	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
V/F	0.9627	likely_pathogenic	0.9562	pathogenic	-1.319	Destabilizing	0.999	D	0.851	deleterious	D	0.585231684	None	None	N
V/G	0.9557	likely_pathogenic	0.9599	pathogenic	-3.149	Highly Destabilizing	1.0	D	0.894	deleterious	D	0.654325283	None	None	N
V/H	0.9993	likely_pathogenic	0.9992	pathogenic	-2.892	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
V/I	0.1113	likely_benign	0.0964	benign	-0.958	Destabilizing	0.767	D	0.328	neutral	D	0.522077333	None	None	N
V/K	0.9985	likely_pathogenic	0.9981	pathogenic	-1.958	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
V/L	0.8197	likely_pathogenic	0.7942	pathogenic	-0.958	Destabilizing	0.981	D	0.687	prob.neutral	D	0.525710998	None	None	N
V/M	0.8596	likely_pathogenic	0.8408	pathogenic	-1.322	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
V/N	0.9937	likely_pathogenic	0.9936	pathogenic	-2.581	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
V/P	0.9975	likely_pathogenic	0.9976	pathogenic	-1.488	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
V/Q	0.9968	likely_pathogenic	0.9965	pathogenic	-2.235	Highly Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
V/R	0.9963	likely_pathogenic	0.9957	pathogenic	-2.005	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
V/S	0.9646	likely_pathogenic	0.9675	pathogenic	-3.059	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
V/T	0.9311	likely_pathogenic	0.9374	pathogenic	-2.618	Highly Destabilizing	0.998	D	0.769	deleterious	None	None	None	None	N
V/W	0.9997	likely_pathogenic	0.9995	pathogenic	-1.832	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
V/Y	0.9972	likely_pathogenic	0.9967	pathogenic	-1.635	Destabilizing	1.0	D	0.859	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.