TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18884	56875;56876;56877	chr2:178599060;178599059;178599058	chr2:179463787;179463786;179463785
N2AB	17243	51952;51953;51954	chr2:178599060;178599059;178599058	chr2:179463787;179463786;179463785
N2A	16316	49171;49172;49173	chr2:178599060;178599059;178599058	chr2:179463787;179463786;179463785
N2B	9819	29680;29681;29682	chr2:178599060;178599059;178599058	chr2:179463787;179463786;179463785
Novex-1	9944	30055;30056;30057	chr2:178599060;178599059;178599058	chr2:179463787;179463786;179463785
Novex-2	10011	30256;30257;30258	chr2:178599060;178599059;178599058	chr2:179463787;179463786;179463785
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: Fn3-25
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.4476
• Predicted PPI site: I

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	0.994	N	0.531	0.274	0.591436515814	gnomAD-4.0.0	7.20496E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.2585E-07	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	0.2498	likely_benign	0.3113	benign	-0.525	Destabilizing	0.997	D	0.457	neutral	N	0.492425564	None	None	I
V/C	0.8238	likely_pathogenic	0.82	pathogenic	-0.638	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
V/D	0.7057	likely_pathogenic	0.7805	pathogenic	-0.271	Destabilizing	0.999	D	0.819	deleterious	N	0.494459789	None	None	I
V/E	0.4187	ambiguous	0.5025	ambiguous	-0.399	Destabilizing	0.999	D	0.816	deleterious	None	None	None	None	I
V/F	0.3781	ambiguous	0.4489	ambiguous	-0.84	Destabilizing	0.999	D	0.667	prob.neutral	N	0.476355534	None	None	I
V/G	0.4901	ambiguous	0.574	pathogenic	-0.634	Destabilizing	0.999	D	0.758	deleterious	N	0.487876424	None	None	I
V/H	0.7758	likely_pathogenic	0.8151	pathogenic	-0.179	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
V/I	0.0807	likely_benign	0.0844	benign	-0.396	Destabilizing	0.994	D	0.531	neutral	N	0.518209443	None	None	I
V/K	0.4332	ambiguous	0.4755	ambiguous	-0.307	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	I
V/L	0.2588	likely_benign	0.303	benign	-0.396	Destabilizing	0.994	D	0.521	neutral	N	0.465213038	None	None	I
V/M	0.2056	likely_benign	0.2586	benign	-0.297	Destabilizing	0.999	D	0.699	prob.delet.	None	None	None	None	I
V/N	0.549	ambiguous	0.6139	pathogenic	-0.087	Destabilizing	0.999	D	0.835	deleterious	None	None	None	None	I
V/P	0.3051	likely_benign	0.3068	benign	-0.405	Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	I
V/Q	0.4232	ambiguous	0.4763	ambiguous	-0.386	Destabilizing	0.999	D	0.842	deleterious	None	None	None	None	I
V/R	0.4425	ambiguous	0.4846	ambiguous	0.236	Stabilizing	0.999	D	0.836	deleterious	None	None	None	None	I
V/S	0.4069	ambiguous	0.4806	ambiguous	-0.462	Destabilizing	0.999	D	0.821	deleterious	None	None	None	None	I
V/T	0.2307	likely_benign	0.2747	benign	-0.493	Destabilizing	0.998	D	0.711	prob.delet.	None	None	None	None	I
V/W	0.946	likely_pathogenic	0.9588	pathogenic	-0.869	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	I
V/Y	0.7933	likely_pathogenic	0.8189	pathogenic	-0.56	Destabilizing	0.999	D	0.712	prob.delet.	None	None	None	None	I

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.