TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24397	73414;73415;73416	chr2:178572943;178572942;178572941	chr2:179437670;179437669;179437668
N2AB	22756	68491;68492;68493	chr2:178572943;178572942;178572941	chr2:179437670;179437669;179437668
N2A	21829	65710;65711;65712	chr2:178572943;178572942;178572941	chr2:179437670;179437669;179437668
N2B	15332	46219;46220;46221	chr2:178572943;178572942;178572941	chr2:179437670;179437669;179437668
Novex-1	15457	46594;46595;46596	chr2:178572943;178572942;178572941	chr2:179437670;179437669;179437668
Novex-2	15524	46795;46796;46797	chr2:178572943;178572942;178572941	chr2:179437670;179437669;179437668
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-65
• Domain position: 75
• Structural Position: 106
• Q(SASA): 0.1319
• 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
I/M	rs1269666445	-1.083	0.884	N	0.687	0.341	0.425851741357	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	5.64E-05	None	0	None	0	0	0
I/M	rs1269666445	-1.083	0.884	N	0.687	0.341	0.425851741357	gnomAD-4.0.0	1.59249E-06	None	None	None	None	N	None	0	0	None	0	2.78753E-05	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
I/A	0.925	likely_pathogenic	0.9166	pathogenic	-2.569	Highly Destabilizing	0.742	D	0.768	deleterious	None	None	None	None	N
I/C	0.8945	likely_pathogenic	0.8835	pathogenic	-1.663	Destabilizing	0.996	D	0.765	deleterious	None	None	None	None	N
I/D	0.9989	likely_pathogenic	0.9984	pathogenic	-3.373	Highly Destabilizing	0.984	D	0.825	deleterious	None	None	None	None	N
I/E	0.9971	likely_pathogenic	0.996	pathogenic	-3.046	Highly Destabilizing	0.984	D	0.826	deleterious	None	None	None	None	N
I/F	0.3526	ambiguous	0.3456	ambiguous	-1.543	Destabilizing	0.015	N	0.382	neutral	N	0.328828741	None	None	N
I/G	0.9859	likely_pathogenic	0.9825	pathogenic	-3.177	Highly Destabilizing	0.953	D	0.799	deleterious	None	None	None	None	N
I/H	0.993	likely_pathogenic	0.9913	pathogenic	-2.887	Highly Destabilizing	0.996	D	0.833	deleterious	None	None	None	None	N
I/K	0.9943	likely_pathogenic	0.9927	pathogenic	-2.107	Highly Destabilizing	0.953	D	0.819	deleterious	None	None	None	None	N
I/L	0.1629	likely_benign	0.1738	benign	-0.745	Destabilizing	0.003	N	0.292	neutral	N	0.460241362	None	None	N
I/M	0.2187	likely_benign	0.2127	benign	-0.776	Destabilizing	0.884	D	0.687	prob.neutral	N	0.517521583	None	None	N
I/N	0.9828	likely_pathogenic	0.9765	pathogenic	-2.867	Highly Destabilizing	0.979	D	0.839	deleterious	N	0.490997658	None	None	N
I/P	0.9936	likely_pathogenic	0.9928	pathogenic	-1.344	Destabilizing	0.984	D	0.835	deleterious	None	None	None	None	N
I/Q	0.9936	likely_pathogenic	0.9917	pathogenic	-2.49	Highly Destabilizing	0.984	D	0.842	deleterious	None	None	None	None	N
I/R	0.9901	likely_pathogenic	0.9872	pathogenic	-2.205	Highly Destabilizing	0.953	D	0.839	deleterious	None	None	None	None	N
I/S	0.9767	likely_pathogenic	0.9712	pathogenic	-3.39	Highly Destabilizing	0.939	D	0.795	deleterious	N	0.490490679	None	None	N
I/T	0.9564	likely_pathogenic	0.9522	pathogenic	-2.895	Highly Destabilizing	0.684	D	0.764	deleterious	N	0.490490679	None	None	N
I/V	0.1283	likely_benign	0.1248	benign	-1.344	Destabilizing	0.028	N	0.207	neutral	N	0.418429238	None	None	N
I/W	0.982	likely_pathogenic	0.9769	pathogenic	-1.962	Destabilizing	0.996	D	0.825	deleterious	None	None	None	None	N
I/Y	0.8964	likely_pathogenic	0.8795	pathogenic	-1.705	Destabilizing	0.835	D	0.75	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.