TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31491	94696;94697;94698	chr2:178547054;178547053;178547052	chr2:179411781;179411780;179411779
N2AB	29850	89773;89774;89775	chr2:178547054;178547053;178547052	chr2:179411781;179411780;179411779
N2A	28923	86992;86993;86994	chr2:178547054;178547053;178547052	chr2:179411781;179411780;179411779
N2B	22426	67501;67502;67503	chr2:178547054;178547053;178547052	chr2:179411781;179411780;179411779
Novex-1	22551	67876;67877;67878	chr2:178547054;178547053;178547052	chr2:179411781;179411780;179411779
Novex-2	22618	68077;68078;68079	chr2:178547054;178547053;178547052	chr2:179411781;179411780;179411779
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: Fn3-117
• Domain position: 84
• Structural Position: 117
• Q(SASA): 0.376
• 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/F	None	None	0.028	N	0.39	0.167	0.717020191167	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-06	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
V/A	0.25	likely_benign	0.2483	benign	-1.531	Destabilizing	0.625	D	0.492	neutral	N	0.458294348	None	None	I
V/C	0.6895	likely_pathogenic	0.6509	pathogenic	-1.005	Destabilizing	0.998	D	0.585	neutral	None	None	None	None	I
V/D	0.6543	likely_pathogenic	0.6551	pathogenic	-0.908	Destabilizing	0.989	D	0.663	neutral	N	0.496716663	None	None	I
V/E	0.4673	ambiguous	0.4594	ambiguous	-0.858	Destabilizing	0.991	D	0.655	neutral	None	None	None	None	I
V/F	0.182	likely_benign	0.1849	benign	-1.067	Destabilizing	0.028	N	0.39	neutral	N	0.466009754	None	None	I
V/G	0.3787	ambiguous	0.3724	ambiguous	-1.899	Destabilizing	0.989	D	0.655	neutral	N	0.478847068	None	None	I
V/H	0.6978	likely_pathogenic	0.6799	pathogenic	-1.307	Destabilizing	0.998	D	0.655	neutral	None	None	None	None	I
V/I	0.0639	likely_benign	0.0647	benign	-0.605	Destabilizing	0.005	N	0.234	neutral	N	0.442940893	None	None	I
V/K	0.5261	ambiguous	0.521	ambiguous	-1.046	Destabilizing	0.974	D	0.659	neutral	None	None	None	None	I
V/L	0.147	likely_benign	0.1341	benign	-0.605	Destabilizing	0.005	N	0.236	neutral	N	0.399419402	None	None	I
V/M	0.1235	likely_benign	0.1225	benign	-0.505	Destabilizing	0.949	D	0.618	neutral	None	None	None	None	I
V/N	0.4	ambiguous	0.3934	ambiguous	-0.918	Destabilizing	0.991	D	0.663	neutral	None	None	None	None	I
V/P	0.4697	ambiguous	0.4074	ambiguous	-0.879	Destabilizing	0.991	D	0.656	neutral	None	None	None	None	I
V/Q	0.4423	ambiguous	0.4134	ambiguous	-1.007	Destabilizing	0.991	D	0.657	neutral	None	None	None	None	I
V/R	0.5138	ambiguous	0.5153	ambiguous	-0.62	Destabilizing	0.991	D	0.661	neutral	None	None	None	None	I
V/S	0.3292	likely_benign	0.3203	benign	-1.584	Destabilizing	0.974	D	0.651	neutral	None	None	None	None	I
V/T	0.2374	likely_benign	0.2429	benign	-1.406	Destabilizing	0.842	D	0.49	neutral	None	None	None	None	I
V/W	0.8141	likely_pathogenic	0.7977	pathogenic	-1.254	Destabilizing	0.998	D	0.669	neutral	None	None	None	None	I
V/Y	0.5327	ambiguous	0.514	ambiguous	-0.943	Destabilizing	0.904	D	0.62	neutral	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.