TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17816	53671;53672;53673	chr2:178607156;178607155;178607154	chr2:179471883;179471882;179471881
N2AB	16175	48748;48749;48750	chr2:178607156;178607155;178607154	chr2:179471883;179471882;179471881
N2A	15248	45967;45968;45969	chr2:178607156;178607155;178607154	chr2:179471883;179471882;179471881
N2B	8751	26476;26477;26478	chr2:178607156;178607155;178607154	chr2:179471883;179471882;179471881
Novex-1	8876	26851;26852;26853	chr2:178607156;178607155;178607154	chr2:179471883;179471882;179471881
Novex-2	8943	27052;27053;27054	chr2:178607156;178607155;178607154	chr2:179471883;179471882;179471881
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-17
• Domain position: 53
• Structural Position: 70
• Q(SASA): 0.7537
• 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
E/G	None	None	0.645	N	0.603	0.356	0.402043589563	gnomAD-4.0.0	2.05356E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69941E-06	0	0
E/V	None	None	0.928	N	0.706	0.487	0.587119504466	gnomAD-4.0.0	6.84519E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16007E-05	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
E/A	0.3107	likely_benign	0.3585	ambiguous	-0.543	Destabilizing	0.645	D	0.634	neutral	N	0.468481949	None	None	N
E/C	0.8939	likely_pathogenic	0.9263	pathogenic	-0.231	Destabilizing	0.995	D	0.735	prob.delet.	None	None	None	None	N
E/D	0.1933	likely_benign	0.1772	benign	-0.572	Destabilizing	0.002	N	0.221	neutral	N	0.479845843	None	None	N
E/F	0.8184	likely_pathogenic	0.8462	pathogenic	-0.1	Destabilizing	0.995	D	0.692	prob.neutral	None	None	None	None	N
E/G	0.4841	ambiguous	0.5219	ambiguous	-0.816	Destabilizing	0.645	D	0.603	neutral	N	0.480598723	None	None	N
E/H	0.7004	likely_pathogenic	0.739	pathogenic	0.017	Stabilizing	0.995	D	0.706	prob.neutral	None	None	None	None	N
E/I	0.4798	ambiguous	0.517	ambiguous	0.17	Stabilizing	0.945	D	0.716	prob.delet.	None	None	None	None	N
E/K	0.47	ambiguous	0.5027	ambiguous	0.129	Stabilizing	0.645	D	0.585	neutral	N	0.50175991	None	None	N
E/L	0.5589	ambiguous	0.6156	pathogenic	0.17	Stabilizing	0.945	D	0.722	prob.delet.	None	None	None	None	N
E/M	0.6164	likely_pathogenic	0.6599	pathogenic	0.299	Stabilizing	0.995	D	0.696	prob.neutral	None	None	None	None	N
E/N	0.4587	ambiguous	0.4687	ambiguous	-0.427	Destabilizing	0.809	D	0.691	prob.neutral	None	None	None	None	N
E/P	0.7407	likely_pathogenic	0.7931	pathogenic	-0.047	Destabilizing	0.945	D	0.75	deleterious	None	None	None	None	N
E/Q	0.3011	likely_benign	0.3385	benign	-0.337	Destabilizing	0.864	D	0.663	neutral	N	0.481457642	None	None	N
E/R	0.6127	likely_pathogenic	0.6576	pathogenic	0.42	Stabilizing	0.945	D	0.716	prob.delet.	None	None	None	None	N
E/S	0.3853	ambiguous	0.4296	ambiguous	-0.595	Destabilizing	0.547	D	0.595	neutral	None	None	None	None	N
E/T	0.3585	ambiguous	0.3945	ambiguous	-0.363	Destabilizing	0.894	D	0.713	prob.delet.	None	None	None	None	N
E/V	0.2921	likely_benign	0.3153	benign	-0.047	Destabilizing	0.928	D	0.706	prob.neutral	N	0.485180625	None	None	N
E/W	0.9458	likely_pathogenic	0.9541	pathogenic	0.159	Stabilizing	0.995	D	0.737	prob.delet.	None	None	None	None	N
E/Y	0.7479	likely_pathogenic	0.7829	pathogenic	0.17	Stabilizing	0.995	D	0.695	prob.neutral	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.