TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5878	17857;17858;17859	chr2:178731033;178731032;178731031	chr2:179595760;179595759;179595758
N2AB	5561	16906;16907;16908	chr2:178731033;178731032;178731031	chr2:179595760;179595759;179595758
N2A	4634	14125;14126;14127	chr2:178731033;178731032;178731031	chr2:179595760;179595759;179595758
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: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-42
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.064
• 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
S/L	None	None	1.0	N	0.789	0.377	0.557637382247	gnomAD-4.0.0	1.59153E-06	None	None	None	None	N	None	0	0	None	0	2.77316E-05	None	0	0	0	0	0
S/P	None	None	1.0	N	0.835	0.377	0.243398259712	gnomAD-4.0.0	1.59154E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85881E-06	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
S/A	0.0969	likely_benign	0.1086	benign	-1.096	Destabilizing	0.997	D	0.599	neutral	N	0.470849852	None	None	N
S/C	0.1476	likely_benign	0.1454	benign	-0.181	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
S/D	0.9712	likely_pathogenic	0.9736	pathogenic	-1.672	Destabilizing	0.999	D	0.654	neutral	None	None	None	None	N
S/E	0.979	likely_pathogenic	0.9834	pathogenic	-1.361	Destabilizing	0.999	D	0.634	neutral	None	None	None	None	N
S/F	0.7261	likely_pathogenic	0.7397	pathogenic	-0.722	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
S/G	0.2061	likely_benign	0.2249	benign	-1.521	Destabilizing	0.999	D	0.642	neutral	None	None	None	None	N
S/H	0.8959	likely_pathogenic	0.8803	pathogenic	-1.356	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
S/I	0.6771	likely_pathogenic	0.7018	pathogenic	0.056	Stabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
S/K	0.9948	likely_pathogenic	0.9957	pathogenic	0.466	Stabilizing	0.999	D	0.651	neutral	None	None	None	None	N
S/L	0.3407	ambiguous	0.3811	ambiguous	0.056	Stabilizing	1.0	D	0.789	deleterious	N	0.461857406	None	None	N
S/M	0.5377	ambiguous	0.5605	ambiguous	-0.409	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
S/N	0.7164	likely_pathogenic	0.725	pathogenic	-0.516	Destabilizing	0.999	D	0.649	neutral	None	None	None	None	N
S/P	0.9461	likely_pathogenic	0.9669	pathogenic	-0.302	Destabilizing	1.0	D	0.835	deleterious	N	0.475659701	None	None	N
S/Q	0.9566	likely_pathogenic	0.9593	pathogenic	-0.056	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
S/R	0.9872	likely_pathogenic	0.9896	pathogenic	-0.208	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
S/T	0.183	likely_benign	0.194	benign	-0.093	Destabilizing	0.999	D	0.609	neutral	N	0.499748607	None	None	N
S/V	0.541	ambiguous	0.5758	pathogenic	-0.302	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
S/W	0.8544	likely_pathogenic	0.8586	pathogenic	-0.968	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
S/Y	0.6741	likely_pathogenic	0.6733	pathogenic	-0.533	Destabilizing	1.0	D	0.85	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.