TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5344	16255;16256;16257	chr2:178733263;178733262;178733261	chr2:179597990;179597989;179597988
N2AB	5027	15304;15305;15306	chr2:178733263;178733262;178733261	chr2:179597990;179597989;179597988
N2A	4100	12523;12524;12525	chr2:178733263;178733262;178733261	chr2:179597990;179597989;179597988
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: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-36
• Domain position: 84
• Structural Position: 169
• Q(SASA): 0.1127
• 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
C/R	None	None	1.0	N	0.907	0.628	0.874387943856	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
C/Y	None	None	1.0	N	0.906	0.401	0.806643597941	gnomAD-4.0.0	1.60987E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4596E-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
C/A	0.3305	likely_benign	0.3665	ambiguous	-1.717	Destabilizing	0.998	D	0.603	neutral	None	None	None	None	N
C/D	0.6642	likely_pathogenic	0.751	pathogenic	0.04	Stabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
C/E	0.7648	likely_pathogenic	0.8362	pathogenic	0.146	Stabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
C/F	0.2793	likely_benign	0.3219	benign	-1.145	Destabilizing	1.0	D	0.905	deleterious	N	0.513115882	None	None	N
C/G	0.1929	likely_benign	0.2107	benign	-2.019	Highly Destabilizing	1.0	D	0.839	deleterious	N	0.492049112	None	None	N
C/H	0.5818	likely_pathogenic	0.6685	pathogenic	-1.924	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
C/I	0.536	ambiguous	0.5983	pathogenic	-0.943	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
C/K	0.8088	likely_pathogenic	0.8648	pathogenic	-0.634	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
C/L	0.507	ambiguous	0.5778	pathogenic	-0.943	Destabilizing	0.999	D	0.666	neutral	None	None	None	None	N
C/M	0.6324	likely_pathogenic	0.6884	pathogenic	-0.125	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
C/N	0.5854	likely_pathogenic	0.659	pathogenic	-0.675	Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
C/P	0.9844	likely_pathogenic	0.9908	pathogenic	-1.175	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
C/Q	0.6126	likely_pathogenic	0.6911	pathogenic	-0.54	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
C/R	0.4577	ambiguous	0.5541	ambiguous	-0.571	Destabilizing	1.0	D	0.907	deleterious	N	0.502809533	None	None	N
C/S	0.2184	likely_benign	0.2394	benign	-1.252	Destabilizing	1.0	D	0.8	deleterious	N	0.50758231	None	None	N
C/T	0.3719	ambiguous	0.4144	ambiguous	-0.949	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
C/V	0.4206	ambiguous	0.4747	ambiguous	-1.175	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
C/W	0.605	likely_pathogenic	0.6828	pathogenic	-1.084	Destabilizing	1.0	D	0.879	deleterious	N	0.510913836	None	None	N
C/Y	0.4228	ambiguous	0.5248	ambiguous	-1.069	Destabilizing	1.0	D	0.906	deleterious	N	0.510406857	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.