TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5883	17872;17873;17874	chr2:178731018;178731017;178731016	chr2:179595745;179595744;179595743
N2AB	5566	16921;16922;16923	chr2:178731018;178731017;178731016	chr2:179595745;179595744;179595743
N2A	4639	14140;14141;14142	chr2:178731018;178731017;178731016	chr2:179595745;179595744;179595743
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-42
• Domain position: 61
• Structural Position: 141
• Q(SASA): 0.2828
• 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/L	rs1468000752	-0.926	None	N	0.061	0.092	0.335910606209	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	2.22618E-04	None	0	None	0	0	0
I/L	rs1468000752	-0.926	None	N	0.061	0.092	0.335910606209	gnomAD-4.0.0	6.36659E-06	None	None	None	None	N	None	0	0	None	0	1.10926E-04	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	0.2037	likely_benign	0.3085	benign	-1.425	Destabilizing	0.055	N	0.378	neutral	None	None	None	None	N
I/C	0.5257	ambiguous	0.6534	pathogenic	-0.913	Destabilizing	0.859	D	0.392	neutral	None	None	None	None	N
I/D	0.4189	ambiguous	0.6574	pathogenic	-0.702	Destabilizing	0.124	N	0.477	neutral	None	None	None	None	N
I/E	0.3946	ambiguous	0.6066	pathogenic	-0.726	Destabilizing	0.22	N	0.487	neutral	None	None	None	None	N
I/F	0.1097	likely_benign	0.1414	benign	-1.016	Destabilizing	0.001	N	0.196	neutral	N	0.47987842	None	None	N
I/G	0.3989	ambiguous	0.563	ambiguous	-1.713	Destabilizing	0.22	N	0.481	neutral	None	None	None	None	N
I/H	0.3054	likely_benign	0.4544	ambiguous	-0.877	Destabilizing	0.667	D	0.467	neutral	None	None	None	None	N
I/K	0.2592	likely_benign	0.4453	ambiguous	-0.884	Destabilizing	0.22	N	0.466	neutral	None	None	None	None	N
I/L	0.0743	likely_benign	0.0853	benign	-0.726	Destabilizing	None	N	0.061	neutral	N	0.421099475	None	None	N
I/M	0.0876	likely_benign	0.1033	benign	-0.57	Destabilizing	0.019	N	0.219	neutral	N	0.447555358	None	None	N
I/N	0.1362	likely_benign	0.2378	benign	-0.67	Destabilizing	0.003	N	0.379	neutral	N	0.423080988	None	None	N
I/P	0.3386	likely_benign	0.4799	ambiguous	-0.926	Destabilizing	0.859	D	0.493	neutral	None	None	None	None	N
I/Q	0.2775	likely_benign	0.4248	ambiguous	-0.882	Destabilizing	0.667	D	0.495	neutral	None	None	None	None	N
I/R	0.192	likely_benign	0.3415	ambiguous	-0.286	Destabilizing	0.667	D	0.499	neutral	None	None	None	None	N
I/S	0.1722	likely_benign	0.2755	benign	-1.297	Destabilizing	0.096	N	0.431	neutral	N	0.424214351	None	None	N
I/T	0.1473	likely_benign	0.2369	benign	-1.207	Destabilizing	0.003	N	0.182	neutral	N	0.43449006	None	None	N
I/V	0.0723	likely_benign	0.0796	benign	-0.926	Destabilizing	None	N	0.121	neutral	N	0.475664679	None	None	N
I/W	0.6209	likely_pathogenic	0.712	pathogenic	-1.029	Destabilizing	0.958	D	0.465	neutral	None	None	None	None	N
I/Y	0.335	likely_benign	0.4362	ambiguous	-0.811	Destabilizing	0.124	N	0.441	neutral	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.