TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21498	64717;64718;64719	chr2:178585252;178585251;178585250	chr2:179449979;179449978;179449977
N2AB	19857	59794;59795;59796	chr2:178585252;178585251;178585250	chr2:179449979;179449978;179449977
N2A	18930	57013;57014;57015	chr2:178585252;178585251;178585250	chr2:179449979;179449978;179449977
N2B	12433	37522;37523;37524	chr2:178585252;178585251;178585250	chr2:179449979;179449978;179449977
Novex-1	12558	37897;37898;37899	chr2:178585252;178585251;178585250	chr2:179449979;179449978;179449977
Novex-2	12625	38098;38099;38100	chr2:178585252;178585251;178585250	chr2:179449979;179449978;179449977
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-124
• Domain position: 30
• Structural Position: 46
• Q(SASA): 0.2783
• 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/Y	rs752724337	-1.732	0.989	N	0.847	0.357	0.697263286892	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	0	None	0	0	1.65893E-04
C/Y	rs752724337	-1.732	0.989	N	0.847	0.357	0.697263286892	gnomAD-4.0.0	1.59235E-05	None	None	None	None	N	None	0	0	None	0	2.49723E-04	None	0	2.41663E-04	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
C/A	0.3843	ambiguous	0.3717	ambiguous	-2.114	Highly Destabilizing	0.525	D	0.59	neutral	None	None	None	None	N
C/D	0.9479	likely_pathogenic	0.9276	pathogenic	-0.532	Destabilizing	0.949	D	0.826	deleterious	None	None	None	None	N
C/E	0.9434	likely_pathogenic	0.924	pathogenic	-0.435	Destabilizing	0.949	D	0.821	deleterious	None	None	None	None	N
C/F	0.3816	ambiguous	0.373	ambiguous	-1.338	Destabilizing	0.989	D	0.848	deleterious	N	0.46689048	None	None	N
C/G	0.3381	likely_benign	0.3122	benign	-2.421	Highly Destabilizing	0.669	D	0.808	deleterious	D	0.532576755	None	None	N
C/H	0.8273	likely_pathogenic	0.7921	pathogenic	-2.155	Highly Destabilizing	0.998	D	0.858	deleterious	None	None	None	None	N
C/I	0.4019	ambiguous	0.4002	ambiguous	-1.31	Destabilizing	0.949	D	0.777	deleterious	None	None	None	None	N
C/K	0.9576	likely_pathogenic	0.9431	pathogenic	-1.355	Destabilizing	0.949	D	0.827	deleterious	None	None	None	None	N
C/L	0.4285	ambiguous	0.417	ambiguous	-1.31	Destabilizing	0.842	D	0.693	prob.neutral	None	None	None	None	N
C/M	0.6044	likely_pathogenic	0.5988	pathogenic	-0.114	Destabilizing	0.998	D	0.763	deleterious	None	None	None	None	N
C/N	0.7839	likely_pathogenic	0.7433	pathogenic	-1.23	Destabilizing	0.949	D	0.823	deleterious	None	None	None	None	N
C/P	0.9148	likely_pathogenic	0.9094	pathogenic	-1.555	Destabilizing	0.974	D	0.85	deleterious	None	None	None	None	N
C/Q	0.8518	likely_pathogenic	0.8214	pathogenic	-1.164	Destabilizing	0.974	D	0.855	deleterious	None	None	None	None	N
C/R	0.8154	likely_pathogenic	0.7784	pathogenic	-1.047	Destabilizing	0.934	D	0.851	deleterious	D	0.532576755	None	None	N
C/S	0.3417	ambiguous	0.3214	benign	-1.851	Destabilizing	0.051	N	0.484	neutral	N	0.484188162	None	None	N
C/T	0.3705	ambiguous	0.3556	ambiguous	-1.578	Destabilizing	0.067	N	0.477	neutral	None	None	None	None	N
C/V	0.2891	likely_benign	0.2944	benign	-1.555	Destabilizing	0.842	D	0.721	prob.delet.	None	None	None	None	N
C/W	0.7453	likely_pathogenic	0.7264	pathogenic	-1.236	Destabilizing	0.997	D	0.849	deleterious	N	0.502947281	None	None	N
C/Y	0.543	ambiguous	0.4994	ambiguous	-1.325	Destabilizing	0.989	D	0.847	deleterious	N	0.457790994	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.