TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7728	23407;23408;23409	chr2:178720580;178720579;178720578	chr2:179585307;179585306;179585305
N2AB	7411	22456;22457;22458	chr2:178720580;178720579;178720578	chr2:179585307;179585306;179585305
N2A	6484	19675;19676;19677	chr2:178720580;178720579;178720578	chr2:179585307;179585306;179585305
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-62
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.6524
• 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
T/A	rs760839592	-0.29	0.847	N	0.551	0.217	0.281381271821	gnomAD-2.1.1	8.07E-06	None	None	None	None	I	None	0	5.81E-05	None	0	0	None	0	None	0	0	0
T/A	rs760839592	-0.29	0.847	N	0.551	0.217	0.281381271821	gnomAD-4.0.0	4.77692E-06	None	None	None	None	I	None	0	6.86342E-05	None	0	0	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	0.2762	likely_benign	0.2843	benign	-0.441	Destabilizing	0.847	D	0.551	neutral	N	0.490730132	None	None	I
T/C	0.8635	likely_pathogenic	0.8791	pathogenic	-0.527	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
T/D	0.6299	likely_pathogenic	0.6202	pathogenic	0.103	Stabilizing	0.997	D	0.639	neutral	None	None	None	None	I
T/E	0.6171	likely_pathogenic	0.6308	pathogenic	0.093	Stabilizing	0.999	D	0.638	neutral	None	None	None	None	I
T/F	0.5865	likely_pathogenic	0.6086	pathogenic	-0.795	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	I
T/G	0.6554	likely_pathogenic	0.6383	pathogenic	-0.624	Destabilizing	0.999	D	0.644	neutral	None	None	None	None	I
T/H	0.5632	ambiguous	0.5849	pathogenic	-0.673	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	I
T/I	0.539	ambiguous	0.6046	pathogenic	-0.061	Destabilizing	1.0	D	0.703	prob.neutral	N	0.505046224	None	None	I
T/K	0.6144	likely_pathogenic	0.6518	pathogenic	-0.394	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	I
T/L	0.2839	likely_benign	0.3004	benign	-0.061	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	I
T/M	0.1777	likely_benign	0.1874	benign	-0.293	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
T/N	0.23	likely_benign	0.2332	benign	-0.414	Destabilizing	0.997	D	0.693	prob.neutral	N	0.475376678	None	None	I
T/P	0.6019	likely_pathogenic	0.6116	pathogenic	-0.158	Destabilizing	0.999	D	0.692	prob.neutral	N	0.489215183	None	None	I
T/Q	0.5212	ambiguous	0.5452	ambiguous	-0.486	Destabilizing	0.999	D	0.698	prob.neutral	None	None	None	None	I
T/R	0.6017	likely_pathogenic	0.6299	pathogenic	-0.13	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
T/S	0.1685	likely_benign	0.1463	benign	-0.628	Destabilizing	0.51	D	0.407	neutral	N	0.437223721	None	None	I
T/V	0.4414	ambiguous	0.4968	ambiguous	-0.158	Destabilizing	0.999	D	0.663	neutral	None	None	None	None	I
T/W	0.8726	likely_pathogenic	0.8735	pathogenic	-0.869	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	I
T/Y	0.6081	likely_pathogenic	0.6295	pathogenic	-0.549	Destabilizing	1.0	D	0.745	deleterious	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.