TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34309	103150;103151;103152	chr2:178533690;178533689;178533688	chr2:179398417;179398416;179398415
N2AB	32668	98227;98228;98229	chr2:178533690;178533689;178533688	chr2:179398417;179398416;179398415
N2A	31741	95446;95447;95448	chr2:178533690;178533689;178533688	chr2:179398417;179398416;179398415
N2B	25244	75955;75956;75957	chr2:178533690;178533689;178533688	chr2:179398417;179398416;179398415
Novex-1	25369	76330;76331;76332	chr2:178533690;178533689;178533688	chr2:179398417;179398416;179398415
Novex-2	25436	76531;76532;76533	chr2:178533690;178533689;178533688	chr2:179398417;179398416;179398415
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-161
• Domain position: 52
• Structural Position: 123
• Q(SASA): 0.187
• 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
F/S	rs776393529	-2.302	0.998	D	0.67	0.591	None	gnomAD-2.1.1	1.07E-05	None	None	None	None	N	None	1.24049E-04	0	None	0	0	None	0	None	0	0	0
F/S	rs776393529	-2.302	0.998	D	0.67	0.591	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
F/S	rs776393529	-2.302	0.998	D	0.67	0.591	None	gnomAD-4.0.0	6.40494E-06	None	None	None	None	N	None	8.46024E-05	0	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
F/A	0.8435	likely_pathogenic	0.8539	pathogenic	-2.133	Highly Destabilizing	0.985	D	0.612	neutral	None	None	None	None	N
F/C	0.6586	likely_pathogenic	0.718	pathogenic	-1.436	Destabilizing	1.0	D	0.728	prob.delet.	N	0.497671426	None	None	N
F/D	0.9784	likely_pathogenic	0.9804	pathogenic	-0.607	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
F/E	0.9561	likely_pathogenic	0.9677	pathogenic	-0.496	Destabilizing	0.999	D	0.776	deleterious	None	None	None	None	N
F/G	0.9648	likely_pathogenic	0.9675	pathogenic	-2.477	Highly Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
F/H	0.8983	likely_pathogenic	0.9004	pathogenic	-0.713	Destabilizing	1.0	D	0.626	neutral	None	None	None	None	N
F/I	0.3113	likely_benign	0.3411	ambiguous	-1.093	Destabilizing	0.925	D	0.445	neutral	N	0.418557816	None	None	N
F/K	0.9634	likely_pathogenic	0.9658	pathogenic	-1.387	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
F/L	0.8983	likely_pathogenic	0.8887	pathogenic	-1.093	Destabilizing	0.031	N	0.163	neutral	N	0.477779478	None	None	N
F/M	0.6366	likely_pathogenic	0.6484	pathogenic	-0.981	Destabilizing	0.991	D	0.505	neutral	None	None	None	None	N
F/N	0.9457	likely_pathogenic	0.9476	pathogenic	-1.522	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
F/P	0.9918	likely_pathogenic	0.9932	pathogenic	-1.435	Destabilizing	0.999	D	0.776	deleterious	None	None	None	None	N
F/Q	0.9401	likely_pathogenic	0.952	pathogenic	-1.487	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
F/R	0.9201	likely_pathogenic	0.9297	pathogenic	-0.843	Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	N
F/S	0.8217	likely_pathogenic	0.8427	pathogenic	-2.365	Highly Destabilizing	0.998	D	0.67	neutral	D	0.530037882	None	None	N
F/T	0.7685	likely_pathogenic	0.7914	pathogenic	-2.148	Highly Destabilizing	0.996	D	0.67	neutral	None	None	None	None	N
F/V	0.3439	ambiguous	0.3696	ambiguous	-1.435	Destabilizing	0.925	D	0.503	neutral	N	0.471965439	None	None	N
F/W	0.6538	likely_pathogenic	0.6535	pathogenic	-0.263	Destabilizing	1.0	D	0.519	neutral	None	None	None	None	N
F/Y	0.3757	ambiguous	0.3579	ambiguous	-0.556	Destabilizing	0.993	D	0.539	neutral	N	0.514780428	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.