TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17392	52399;52400;52401	chr2:178608837;178608836;178608835	chr2:179473564;179473563;179473562
N2AB	15751	47476;47477;47478	chr2:178608837;178608836;178608835	chr2:179473564;179473563;179473562
N2A	14824	44695;44696;44697	chr2:178608837;178608836;178608835	chr2:179473564;179473563;179473562
N2B	8327	25204;25205;25206	chr2:178608837;178608836;178608835	chr2:179473564;179473563;179473562
Novex-1	8452	25579;25580;25581	chr2:178608837;178608836;178608835	chr2:179473564;179473563;179473562
Novex-2	8519	25780;25781;25782	chr2:178608837;178608836;178608835	chr2:179473564;179473563;179473562
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-14
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.5042
• Predicted PPI site: I

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
P/T	None	None	1.0	N	0.873	0.603	0.445107144611	gnomAD-4.0.0	1.36961E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.31922E-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
P/A	0.1129	likely_benign	0.111	benign	-1.849	Destabilizing	1.0	D	0.82	deleterious	N	0.507189947	None	None	I
P/C	0.7408	likely_pathogenic	0.7388	pathogenic	-1.172	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
P/D	0.8242	likely_pathogenic	0.8391	pathogenic	-2.289	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
P/E	0.5131	ambiguous	0.5344	ambiguous	-2.164	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	I
P/F	0.7885	likely_pathogenic	0.8019	pathogenic	-1.271	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
P/G	0.6493	likely_pathogenic	0.6608	pathogenic	-2.248	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	I
P/H	0.5156	ambiguous	0.5309	ambiguous	-1.731	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	I
P/I	0.4997	ambiguous	0.4908	ambiguous	-0.782	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	I
P/K	0.4858	ambiguous	0.5144	ambiguous	-1.663	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
P/L	0.2533	likely_benign	0.2433	benign	-0.782	Destabilizing	1.0	D	0.881	deleterious	N	0.518144495	None	None	I
P/M	0.4374	ambiguous	0.4421	ambiguous	-0.64	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
P/N	0.7196	likely_pathogenic	0.7274	pathogenic	-1.725	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	I
P/Q	0.3396	likely_benign	0.3488	ambiguous	-1.756	Destabilizing	1.0	D	0.89	deleterious	N	0.491077018	None	None	I
P/R	0.4142	ambiguous	0.4461	ambiguous	-1.234	Destabilizing	1.0	D	0.887	deleterious	N	0.487772108	None	None	I
P/S	0.3387	likely_benign	0.3353	benign	-2.211	Highly Destabilizing	1.0	D	0.871	deleterious	N	0.493772816	None	None	I
P/T	0.3103	likely_benign	0.3083	benign	-1.967	Destabilizing	1.0	D	0.873	deleterious	N	0.49978675	None	None	I
P/V	0.3566	ambiguous	0.3506	ambiguous	-1.11	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	I
P/W	0.9227	likely_pathogenic	0.9304	pathogenic	-1.607	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	I
P/Y	0.7572	likely_pathogenic	0.7754	pathogenic	-1.263	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	I

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.