TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17661	53206;53207;53208	chr2:178607806;178607805;178607804	chr2:179472533;179472532;179472531
N2AB	16020	48283;48284;48285	chr2:178607806;178607805;178607804	chr2:179472533;179472532;179472531
N2A	15093	45502;45503;45504	chr2:178607806;178607805;178607804	chr2:179472533;179472532;179472531
N2B	8596	26011;26012;26013	chr2:178607806;178607805;178607804	chr2:179472533;179472532;179472531
Novex-1	8721	26386;26387;26388	chr2:178607806;178607805;178607804	chr2:179472533;179472532;179472531
Novex-2	8788	26587;26588;26589	chr2:178607806;178607805;178607804	chr2:179472533;179472532;179472531
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-16
• Domain position: 93
• Structural Position: 127
• Q(SASA): 0.3394
• 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/D	None	None	0.981	N	0.857	0.244	0.626665467207	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.3363	likely_benign	0.2432	benign	-1.758	Destabilizing	0.022	N	0.329	neutral	N	0.457364409	None	None	N
V/C	0.7521	likely_pathogenic	0.7083	pathogenic	-1.315	Destabilizing	0.999	D	0.67	prob.neutral	None	None	None	None	N
V/D	0.7704	likely_pathogenic	0.6886	pathogenic	-1.65	Destabilizing	0.981	D	0.857	deleterious	N	0.478510538	None	None	N
V/E	0.54	ambiguous	0.4605	ambiguous	-1.551	Destabilizing	0.971	D	0.785	deleterious	None	None	None	None	N
V/F	0.2577	likely_benign	0.2257	benign	-1.132	Destabilizing	0.961	D	0.676	prob.neutral	N	0.475215174	None	None	N
V/G	0.5009	ambiguous	0.4205	ambiguous	-2.197	Highly Destabilizing	0.926	D	0.806	deleterious	N	0.466393764	None	None	N
V/H	0.7683	likely_pathogenic	0.7169	pathogenic	-1.747	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
V/I	0.0797	likely_benign	0.0776	benign	-0.606	Destabilizing	0.022	N	0.269	neutral	N	0.500788757	None	None	N
V/K	0.5274	ambiguous	0.4674	ambiguous	-1.542	Destabilizing	0.971	D	0.78	deleterious	None	None	None	None	N
V/L	0.2564	likely_benign	0.235	benign	-0.606	Destabilizing	0.595	D	0.39	neutral	N	0.500788757	None	None	N
V/M	0.1816	likely_benign	0.1661	benign	-0.524	Destabilizing	0.971	D	0.546	neutral	None	None	None	None	N
V/N	0.6208	likely_pathogenic	0.5511	ambiguous	-1.51	Destabilizing	0.985	D	0.861	deleterious	None	None	None	None	N
V/P	0.9577	likely_pathogenic	0.9317	pathogenic	-0.956	Destabilizing	0.985	D	0.803	deleterious	None	None	None	None	N
V/Q	0.4982	ambiguous	0.4508	ambiguous	-1.522	Destabilizing	0.985	D	0.811	deleterious	None	None	None	None	N
V/R	0.472	ambiguous	0.4224	ambiguous	-1.163	Destabilizing	0.985	D	0.858	deleterious	None	None	None	None	N
V/S	0.4898	ambiguous	0.406	ambiguous	-2.141	Highly Destabilizing	0.943	D	0.758	deleterious	None	None	None	None	N
V/T	0.2949	likely_benign	0.2565	benign	-1.904	Destabilizing	0.904	D	0.563	neutral	None	None	None	None	N
V/W	0.895	likely_pathogenic	0.8749	pathogenic	-1.437	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
V/Y	0.6964	likely_pathogenic	0.6367	pathogenic	-1.112	Destabilizing	0.995	D	0.663	prob.neutral	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.