TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14330	43213;43214;43215	chr2:178633285;178633284;178633283	chr2:179498012;179498011;179498010
N2AB	12689	38290;38291;38292	chr2:178633285;178633284;178633283	chr2:179498012;179498011;179498010
N2A	11762	35509;35510;35511	chr2:178633285;178633284;178633283	chr2:179498012;179498011;179498010
N2B	5265	16018;16019;16020	chr2:178633285;178633284;178633283	chr2:179498012;179498011;179498010
Novex-1	5390	16393;16394;16395	chr2:178633285;178633284;178633283	chr2:179498012;179498011;179498010
Novex-2	5457	16594;16595;16596	chr2:178633285;178633284;178633283	chr2:179498012;179498011;179498010
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-94
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.1037
• 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/M	rs2060028411	None	0.005	D	0.441	0.169	0.0611884634855	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/M	rs2060028411	None	0.005	D	0.441	0.169	0.0611884634855	gnomAD-4.0.0	6.57445E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.4708E-05	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	0.4644	ambiguous	0.4245	ambiguous	-1.968	Destabilizing	0.025	N	0.443	neutral	N	0.425901956	None	None	N
V/C	0.827	likely_pathogenic	0.7674	pathogenic	-1.333	Destabilizing	0.869	D	0.542	neutral	None	None	None	None	N
V/D	0.8785	likely_pathogenic	0.8591	pathogenic	-2.366	Highly Destabilizing	0.637	D	0.739	deleterious	None	None	None	None	N
V/E	0.7858	likely_pathogenic	0.777	pathogenic	-2.221	Highly Destabilizing	0.303	N	0.641	neutral	D	0.62920156	None	None	N
V/F	0.5276	ambiguous	0.5088	ambiguous	-1.213	Destabilizing	0.125	N	0.697	prob.delet.	None	None	None	None	N
V/G	0.5005	ambiguous	0.4707	ambiguous	-2.423	Highly Destabilizing	0.303	N	0.719	prob.delet.	D	0.590850684	None	None	N
V/H	0.9326	likely_pathogenic	0.9072	pathogenic	-2.09	Highly Destabilizing	0.869	D	0.637	neutral	None	None	None	None	N
V/I	0.1158	likely_benign	0.1057	benign	-0.735	Destabilizing	0.001	N	0.213	neutral	None	None	None	None	N
V/K	0.7607	likely_pathogenic	0.7197	pathogenic	-1.61	Destabilizing	0.221	N	0.661	prob.neutral	None	None	None	None	N
V/L	0.2559	likely_benign	0.17	benign	-0.735	Destabilizing	None	N	0.095	neutral	N	0.437243363	None	None	N
V/M	0.3777	ambiguous	0.3404	ambiguous	-0.669	Destabilizing	0.005	N	0.441	neutral	D	0.630126083	None	None	N
V/N	0.7498	likely_pathogenic	0.7096	pathogenic	-1.712	Destabilizing	0.366	N	0.732	deleterious	None	None	None	None	N
V/P	0.9604	likely_pathogenic	0.9514	pathogenic	-1.117	Destabilizing	0.637	D	0.677	prob.neutral	None	None	None	None	N
V/Q	0.7879	likely_pathogenic	0.7504	pathogenic	-1.687	Destabilizing	0.366	N	0.661	prob.neutral	None	None	None	None	N
V/R	0.6928	likely_pathogenic	0.6379	pathogenic	-1.28	Destabilizing	0.366	N	0.741	deleterious	None	None	None	None	N
V/S	0.6516	likely_pathogenic	0.6248	pathogenic	-2.288	Highly Destabilizing	0.075	N	0.639	neutral	None	None	None	None	N
V/T	0.4691	ambiguous	0.434	ambiguous	-2.026	Highly Destabilizing	0.075	N	0.563	neutral	None	None	None	None	N
V/W	0.9643	likely_pathogenic	0.9431	pathogenic	-1.663	Destabilizing	0.869	D	0.663	prob.neutral	None	None	None	None	N
V/Y	0.8685	likely_pathogenic	0.834	pathogenic	-1.312	Destabilizing	0.366	N	0.699	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.