TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27654	83185;83186;83187	chr2:178563172;178563171;178563170	chr2:179427899;179427898;179427897
N2AB	26013	78262;78263;78264	chr2:178563172;178563171;178563170	chr2:179427899;179427898;179427897
N2A	25086	75481;75482;75483	chr2:178563172;178563171;178563170	chr2:179427899;179427898;179427897
N2B	18589	55990;55991;55992	chr2:178563172;178563171;178563170	chr2:179427899;179427898;179427897
Novex-1	18714	56365;56366;56367	chr2:178563172;178563171;178563170	chr2:179427899;179427898;179427897
Novex-2	18781	56566;56567;56568	chr2:178563172;178563171;178563170	chr2:179427899;179427898;179427897
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: Fn3-89
• Domain position: 85
• Structural Position: 117
• Q(SASA): 0.3842
• 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	rs1027584774	None	0.014	N	0.323	0.067	0.254761474806	gnomAD-4.0.0	6.36557E-06	None	None	None	None	I	None	0	0	None	0	5.54539E-05	None	0	0	0	0	6.04887E-05

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	0.125	likely_benign	0.1364	benign	-0.731	Destabilizing	0.058	N	0.384	neutral	N	0.492502922	None	None	I
V/C	0.6787	likely_pathogenic	0.7129	pathogenic	-0.69	Destabilizing	0.998	D	0.757	deleterious	None	None	None	None	I
V/D	0.4563	ambiguous	0.47	ambiguous	-0.314	Destabilizing	0.978	D	0.815	deleterious	None	None	None	None	I
V/E	0.2954	likely_benign	0.3077	benign	-0.415	Destabilizing	0.97	D	0.811	deleterious	N	0.501871767	None	None	I
V/F	0.1517	likely_benign	0.158	benign	-0.832	Destabilizing	0.956	D	0.769	deleterious	None	None	None	None	I
V/G	0.2734	likely_benign	0.2741	benign	-0.901	Destabilizing	0.89	D	0.771	deleterious	N	0.486911691	None	None	I
V/H	0.5696	likely_pathogenic	0.5983	pathogenic	-0.375	Destabilizing	0.998	D	0.815	deleterious	None	None	None	None	I
V/I	0.0635	likely_benign	0.0676	benign	-0.421	Destabilizing	0.014	N	0.323	neutral	N	0.499506252	None	None	I
V/K	0.3107	likely_benign	0.3218	benign	-0.542	Destabilizing	0.956	D	0.812	deleterious	None	None	None	None	I
V/L	0.1491	likely_benign	0.1722	benign	-0.421	Destabilizing	0.014	N	0.325	neutral	N	0.455446044	None	None	I
V/M	0.1155	likely_benign	0.129	benign	-0.382	Destabilizing	0.956	D	0.714	prob.delet.	None	None	None	None	I
V/N	0.3203	likely_benign	0.3572	ambiguous	-0.251	Destabilizing	0.993	D	0.817	deleterious	None	None	None	None	I
V/P	0.3155	likely_benign	0.3491	ambiguous	-0.488	Destabilizing	0.978	D	0.815	deleterious	None	None	None	None	I
V/Q	0.3056	likely_benign	0.3332	benign	-0.512	Destabilizing	0.993	D	0.819	deleterious	None	None	None	None	I
V/R	0.2709	likely_benign	0.2822	benign	0.015	Stabilizing	0.978	D	0.816	deleterious	None	None	None	None	I
V/S	0.2195	likely_benign	0.2343	benign	-0.692	Destabilizing	0.915	D	0.771	deleterious	None	None	None	None	I
V/T	0.1264	likely_benign	0.1429	benign	-0.688	Destabilizing	0.86	D	0.645	neutral	None	None	None	None	I
V/W	0.7221	likely_pathogenic	0.7315	pathogenic	-0.878	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	I
V/Y	0.5147	ambiguous	0.5399	ambiguous	-0.591	Destabilizing	0.978	D	0.768	deleterious	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.