TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24368	73327;73328;73329	chr2:178573030;178573029;178573028	chr2:179437757;179437756;179437755
N2AB	22727	68404;68405;68406	chr2:178573030;178573029;178573028	chr2:179437757;179437756;179437755
N2A	21800	65623;65624;65625	chr2:178573030;178573029;178573028	chr2:179437757;179437756;179437755
N2B	15303	46132;46133;46134	chr2:178573030;178573029;178573028	chr2:179437757;179437756;179437755
Novex-1	15428	46507;46508;46509	chr2:178573030;178573029;178573028	chr2:179437757;179437756;179437755
Novex-2	15495	46708;46709;46710	chr2:178573030;178573029;178573028	chr2:179437757;179437756;179437755
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-65
• Domain position: 46
• Structural Position: 63
• Q(SASA): 1.0174
• 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
D/H	None	None	0.999	N	0.72	0.381	0.425028116352	gnomAD-4.0.0	6.84511E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65761E-05
D/N	None	None	0.998	N	0.688	0.306	0.327952845175	gnomAD-4.0.0	1.36902E-06	None	None	None	None	N	None	5.98086E-05	0	None	0	0	None	0	0	0	0	0
D/Y	rs886042474	None	0.998	N	0.741	0.43	0.654079243945	gnomAD-4.0.0	6.84511E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99701E-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
D/A	0.111	likely_benign	0.1113	benign	-0.364	Destabilizing	0.919	D	0.609	neutral	N	0.48074992	None	None	N
D/C	0.4606	ambiguous	0.4655	ambiguous	-0.287	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
D/E	0.0802	likely_benign	0.0845	benign	-0.347	Destabilizing	0.979	D	0.533	neutral	N	0.418525238	None	None	N
D/F	0.5048	ambiguous	0.5055	ambiguous	-0.115	Destabilizing	0.991	D	0.748	deleterious	None	None	None	None	N
D/G	0.0948	likely_benign	0.0948	benign	-0.572	Destabilizing	0.979	D	0.641	neutral	N	0.44476769	None	None	N
D/H	0.233	likely_benign	0.2326	benign	0.256	Stabilizing	0.999	D	0.72	prob.delet.	N	0.481484096	None	None	N
D/I	0.2421	likely_benign	0.2428	benign	0.146	Stabilizing	0.982	D	0.677	prob.neutral	None	None	None	None	N
D/K	0.189	likely_benign	0.188	benign	0.097	Stabilizing	0.995	D	0.707	prob.neutral	None	None	None	None	N
D/L	0.2656	likely_benign	0.2601	benign	0.146	Stabilizing	0.982	D	0.661	neutral	None	None	None	None	N
D/M	0.363	ambiguous	0.3699	ambiguous	0.113	Stabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
D/N	0.084	likely_benign	0.0845	benign	-0.292	Destabilizing	0.998	D	0.688	prob.neutral	N	0.479997771	None	None	N
D/P	0.4298	ambiguous	0.4332	ambiguous	-0.003	Destabilizing	0.998	D	0.711	prob.delet.	None	None	None	None	N
D/Q	0.1977	likely_benign	0.202	benign	-0.233	Destabilizing	0.998	D	0.729	prob.delet.	None	None	None	None	N
D/R	0.2592	likely_benign	0.2537	benign	0.445	Stabilizing	0.995	D	0.741	deleterious	None	None	None	None	N
D/S	0.0983	likely_benign	0.1022	benign	-0.413	Destabilizing	0.995	D	0.658	neutral	None	None	None	None	N
D/T	0.1363	likely_benign	0.1402	benign	-0.241	Destabilizing	0.991	D	0.675	neutral	None	None	None	None	N
D/V	0.1446	likely_benign	0.1416	benign	-0.003	Destabilizing	0.142	N	0.601	neutral	N	0.50418414	None	None	N
D/W	0.7678	likely_pathogenic	0.7645	pathogenic	0.07	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
D/Y	0.204	likely_benign	0.1967	benign	0.131	Stabilizing	0.998	D	0.741	deleterious	N	0.474393751	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.