TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27489	82690;82691;82692	chr2:178563667;178563666;178563665	chr2:179428394;179428393;179428392
N2AB	25848	77767;77768;77769	chr2:178563667;178563666;178563665	chr2:179428394;179428393;179428392
N2A	24921	74986;74987;74988	chr2:178563667;178563666;178563665	chr2:179428394;179428393;179428392
N2B	18424	55495;55496;55497	chr2:178563667;178563666;178563665	chr2:179428394;179428393;179428392
Novex-1	18549	55870;55871;55872	chr2:178563667;178563666;178563665	chr2:179428394;179428393;179428392
Novex-2	18616	56071;56072;56073	chr2:178563667;178563666;178563665	chr2:179428394;179428393;179428392
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-88
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.2346
• 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
T/I	None	None	0.125	N	0.373	0.318	0.349870743963	gnomAD-4.0.0	1.59119E-06	None	None	None	None	N	None	0	0	None	0	2.77346E-05	None	0	0	0	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
T/A	0.0967	likely_benign	0.1249	benign	-0.927	Destabilizing	0.489	N	0.414	neutral	N	0.506456441	None	None	N
T/C	0.3087	likely_benign	0.3568	ambiguous	-0.657	Destabilizing	0.998	D	0.639	neutral	None	None	None	None	N
T/D	0.625	likely_pathogenic	0.7038	pathogenic	-0.862	Destabilizing	0.956	D	0.583	neutral	None	None	None	None	N
T/E	0.5222	ambiguous	0.5848	pathogenic	-0.715	Destabilizing	0.956	D	0.581	neutral	None	None	None	None	N
T/F	0.2869	likely_benign	0.3556	ambiguous	-0.611	Destabilizing	0.956	D	0.699	prob.neutral	None	None	None	None	N
T/G	0.2521	likely_benign	0.3368	benign	-1.317	Destabilizing	0.754	D	0.581	neutral	None	None	None	None	N
T/H	0.3312	likely_benign	0.3647	ambiguous	-1.49	Destabilizing	0.998	D	0.724	prob.delet.	None	None	None	None	N
T/I	0.2086	likely_benign	0.25	benign	0.07	Stabilizing	0.125	N	0.373	neutral	N	0.494894771	None	None	N
T/K	0.3979	ambiguous	0.434	ambiguous	-0.613	Destabilizing	0.942	D	0.578	neutral	N	0.519847026	None	None	N
T/L	0.1117	likely_benign	0.1319	benign	0.07	Stabilizing	0.303	N	0.459	neutral	None	None	None	None	N
T/M	0.0962	likely_benign	0.1049	benign	0.032	Stabilizing	0.559	D	0.443	neutral	None	None	None	None	N
T/N	0.156	likely_benign	0.1871	benign	-1.057	Destabilizing	0.956	D	0.473	neutral	None	None	None	None	N
T/P	0.6342	likely_pathogenic	0.7192	pathogenic	-0.229	Destabilizing	0.97	D	0.615	neutral	D	0.524355331	None	None	N
T/Q	0.3267	likely_benign	0.3536	ambiguous	-0.913	Destabilizing	0.956	D	0.619	neutral	None	None	None	None	N
T/R	0.3329	likely_benign	0.3663	ambiguous	-0.711	Destabilizing	0.942	D	0.613	neutral	D	0.524444769	None	None	N
T/S	0.1075	likely_benign	0.1287	benign	-1.304	Destabilizing	0.058	N	0.414	neutral	N	0.432742542	None	None	N
T/V	0.1494	likely_benign	0.1792	benign	-0.229	Destabilizing	0.559	D	0.424	neutral	None	None	None	None	N
T/W	0.6885	likely_pathogenic	0.7502	pathogenic	-0.714	Destabilizing	0.998	D	0.764	deleterious	None	None	None	None	N
T/Y	0.3585	ambiguous	0.4136	ambiguous	-0.367	Destabilizing	0.978	D	0.734	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.