TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17421	52486;52487;52488	chr2:178608750;178608749;178608748	chr2:179473477;179473476;179473475
N2AB	15780	47563;47564;47565	chr2:178608750;178608749;178608748	chr2:179473477;179473476;179473475
N2A	14853	44782;44783;44784	chr2:178608750;178608749;178608748	chr2:179473477;179473476;179473475
N2B	8356	25291;25292;25293	chr2:178608750;178608749;178608748	chr2:179473477;179473476;179473475
Novex-1	8481	25666;25667;25668	chr2:178608750;178608749;178608748	chr2:179473477;179473476;179473475
Novex-2	8548	25867;25868;25869	chr2:178608750;178608749;178608748	chr2:179473477;179473476;179473475
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: Fn3-14
• Domain position: 53
• Structural Position: 68
• Q(SASA): 0.16
• 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/F	rs1340432964	None	0.638	N	0.795	0.303	0.501624679856	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/F	rs1340432964	None	0.638	N	0.795	0.303	0.501624679856	gnomAD-4.0.0	8.06204E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.01761E-05	0	1.60298E-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	0.6216	likely_pathogenic	0.5538	ambiguous	-1.431	Destabilizing	0.334	N	0.46	neutral	N	0.502973419	None	None	N
V/C	0.8809	likely_pathogenic	0.8668	pathogenic	-1.014	Destabilizing	0.982	D	0.794	deleterious	None	None	None	None	N
V/D	0.9762	likely_pathogenic	0.9733	pathogenic	-1.272	Destabilizing	0.781	D	0.812	deleterious	N	0.509578757	None	None	N
V/E	0.9335	likely_pathogenic	0.9315	pathogenic	-1.17	Destabilizing	0.826	D	0.769	deleterious	None	None	None	None	N
V/F	0.6141	likely_pathogenic	0.5912	pathogenic	-0.886	Destabilizing	0.638	D	0.795	deleterious	N	0.482356242	None	None	N
V/G	0.8511	likely_pathogenic	0.8074	pathogenic	-1.841	Destabilizing	0.781	D	0.783	deleterious	N	0.487119636	None	None	N
V/H	0.9726	likely_pathogenic	0.9699	pathogenic	-1.345	Destabilizing	0.982	D	0.803	deleterious	None	None	None	None	N
V/I	0.084	likely_benign	0.0905	benign	-0.367	Destabilizing	0.002	N	0.239	neutral	N	0.492583067	None	None	N
V/K	0.9621	likely_pathogenic	0.9577	pathogenic	-1.229	Destabilizing	0.826	D	0.779	deleterious	None	None	None	None	N
V/L	0.3905	ambiguous	0.4072	ambiguous	-0.367	Destabilizing	0.034	N	0.403	neutral	N	0.458027776	None	None	N
V/M	0.3999	ambiguous	0.3726	ambiguous	-0.363	Destabilizing	0.7	D	0.695	prob.neutral	None	None	None	None	N
V/N	0.9133	likely_pathogenic	0.9083	pathogenic	-1.292	Destabilizing	0.935	D	0.817	deleterious	None	None	None	None	N
V/P	0.9664	likely_pathogenic	0.9617	pathogenic	-0.688	Destabilizing	0.935	D	0.804	deleterious	None	None	None	None	N
V/Q	0.9198	likely_pathogenic	0.9137	pathogenic	-1.28	Destabilizing	0.935	D	0.807	deleterious	None	None	None	None	N
V/R	0.9502	likely_pathogenic	0.9477	pathogenic	-0.889	Destabilizing	0.826	D	0.819	deleterious	None	None	None	None	N
V/S	0.8062	likely_pathogenic	0.7724	pathogenic	-1.885	Destabilizing	0.826	D	0.757	deleterious	None	None	None	None	N
V/T	0.6406	likely_pathogenic	0.5958	pathogenic	-1.647	Destabilizing	0.399	N	0.563	neutral	None	None	None	None	N
V/W	0.9867	likely_pathogenic	0.9856	pathogenic	-1.207	Destabilizing	0.982	D	0.784	deleterious	None	None	None	None	N
V/Y	0.9403	likely_pathogenic	0.9389	pathogenic	-0.829	Destabilizing	0.826	D	0.81	deleterious	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.