TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13944	42055;42056;42057	chr2:178635494;178635493;178635492	chr2:179500221;179500220;179500219
N2AB	12303	37132;37133;37134	chr2:178635494;178635493;178635492	chr2:179500221;179500220;179500219
N2A	11376	34351;34352;34353	chr2:178635494;178635493;178635492	chr2:179500221;179500220;179500219
N2B	4879	14860;14861;14862	chr2:178635494;178635493;178635492	chr2:179500221;179500220;179500219
Novex-1	5004	15235;15236;15237	chr2:178635494;178635493;178635492	chr2:179500221;179500220;179500219
Novex-2	5071	15436;15437;15438	chr2:178635494;178635493;178635492	chr2:179500221;179500220;179500219
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: Ig-89
• Domain position: 69
• Structural Position: 153
• Q(SASA): 0.3196
• 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/V	None	None	0.999	N	0.778	0.521	0.423836183345	gnomAD-4.0.0	1.61311E-06	None	None	None	None	N	None	0	2.34973E-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
E/A	0.6234	likely_pathogenic	0.5138	ambiguous	-0.938	Destabilizing	0.997	D	0.744	deleterious	D	0.526192305	None	None	N
E/C	0.9886	likely_pathogenic	0.981	pathogenic	-0.464	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/D	0.2748	likely_benign	0.1928	benign	-1.075	Destabilizing	0.997	D	0.671	prob.neutral	D	0.52714921	None	None	N
E/F	0.9757	likely_pathogenic	0.9645	pathogenic	-0.307	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
E/G	0.7372	likely_pathogenic	0.653	pathogenic	-1.312	Destabilizing	0.999	D	0.73	deleterious	D	0.529612131	None	None	N
E/H	0.9446	likely_pathogenic	0.9082	pathogenic	-0.512	Destabilizing	1.0	D	0.692	prob.delet.	None	None	None	None	N
E/I	0.8454	likely_pathogenic	0.7748	pathogenic	0.087	Stabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
E/K	0.801	likely_pathogenic	0.6754	pathogenic	-0.514	Destabilizing	0.997	D	0.727	deleterious	D	0.523599715	None	None	N
E/L	0.8921	likely_pathogenic	0.8335	pathogenic	0.087	Stabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
E/M	0.9089	likely_pathogenic	0.8673	pathogenic	0.522	Stabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
E/N	0.7537	likely_pathogenic	0.6004	pathogenic	-1.046	Destabilizing	0.999	D	0.731	deleterious	None	None	None	None	N
E/P	0.9187	likely_pathogenic	0.8578	pathogenic	-0.234	Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
E/Q	0.6171	likely_pathogenic	0.5038	ambiguous	-0.915	Destabilizing	0.999	D	0.706	prob.delet.	N	0.485452218	None	None	N
E/R	0.8787	likely_pathogenic	0.8109	pathogenic	-0.215	Destabilizing	0.999	D	0.737	deleterious	None	None	None	None	N
E/S	0.6676	likely_pathogenic	0.5517	ambiguous	-1.373	Destabilizing	0.998	D	0.719	prob.delet.	None	None	None	None	N
E/T	0.6848	likely_pathogenic	0.5507	ambiguous	-1.056	Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
E/V	0.7063	likely_pathogenic	0.5903	pathogenic	-0.234	Destabilizing	0.999	D	0.778	deleterious	N	0.517091842	None	None	N
E/W	0.992	likely_pathogenic	0.9889	pathogenic	None	Stabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
E/Y	0.9544	likely_pathogenic	0.9286	pathogenic	-0.023	Destabilizing	1.0	D	0.823	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.