TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19121	57586;57587;57588	chr2:178597721;178597720;178597719	chr2:179462448;179462447;179462446
N2AB	17480	52663;52664;52665	chr2:178597721;178597720;178597719	chr2:179462448;179462447;179462446
N2A	16553	49882;49883;49884	chr2:178597721;178597720;178597719	chr2:179462448;179462447;179462446
N2B	10056	30391;30392;30393	chr2:178597721;178597720;178597719	chr2:179462448;179462447;179462446
Novex-1	10181	30766;30767;30768	chr2:178597721;178597720;178597719	chr2:179462448;179462447;179462446
Novex-2	10248	30967;30968;30969	chr2:178597721;178597720;178597719	chr2:179462448;179462447;179462446
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-117
• Domain position: 27
• Structural Position: 43
• Q(SASA): 0.5835
• 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/L	rs779397487	None	0.801	N	0.459	0.349	0.565168447923	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/L	rs779397487	None	0.801	N	0.459	0.349	0.565168447923	gnomAD-4.0.0	6.57739E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47067E-05	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
P/A	0.0496	likely_benign	0.0525	benign	-0.49	Destabilizing	0.002	N	0.241	neutral	N	0.439301234	None	None	I
P/C	0.4271	ambiguous	0.4272	ambiguous	-0.657	Destabilizing	0.998	D	0.505	neutral	None	None	None	None	I
P/D	0.3823	ambiguous	0.4329	ambiguous	-0.398	Destabilizing	0.842	D	0.389	neutral	None	None	None	None	I
P/E	0.2103	likely_benign	0.2493	benign	-0.522	Destabilizing	0.728	D	0.373	neutral	None	None	None	None	I
P/F	0.3472	ambiguous	0.382	ambiguous	-0.773	Destabilizing	0.974	D	0.507	neutral	None	None	None	None	I
P/G	0.3064	likely_benign	0.3197	benign	-0.601	Destabilizing	0.728	D	0.441	neutral	None	None	None	None	I
P/H	0.1791	likely_benign	0.213	benign	-0.178	Destabilizing	0.991	D	0.495	neutral	N	0.521861116	None	None	I
P/I	0.1464	likely_benign	0.1613	benign	-0.351	Destabilizing	0.949	D	0.505	neutral	None	None	None	None	I
P/K	0.2281	likely_benign	0.2727	benign	-0.473	Destabilizing	0.728	D	0.355	neutral	None	None	None	None	I
P/L	0.0808	likely_benign	0.0892	benign	-0.351	Destabilizing	0.801	D	0.459	neutral	N	0.473125806	None	None	I
P/M	0.1783	likely_benign	0.184	benign	-0.396	Destabilizing	0.998	D	0.497	neutral	None	None	None	None	I
P/N	0.2474	likely_benign	0.2559	benign	-0.214	Destabilizing	0.974	D	0.494	neutral	None	None	None	None	I
P/Q	0.1153	likely_benign	0.1386	benign	-0.479	Destabilizing	0.325	N	0.265	neutral	None	None	None	None	I
P/R	0.1841	likely_benign	0.2328	benign	0.073	Stabilizing	0.934	D	0.471	neutral	N	0.48390016	None	None	I
P/S	0.0899	likely_benign	0.0954	benign	-0.543	Destabilizing	0.669	D	0.353	neutral	N	0.501965846	None	None	I
P/T	0.0716	likely_benign	0.0758	benign	-0.571	Destabilizing	0.801	D	0.359	neutral	N	0.433124623	None	None	I
P/V	0.1024	likely_benign	0.1097	benign	-0.364	Destabilizing	0.728	D	0.452	neutral	None	None	None	None	I
P/W	0.6394	likely_pathogenic	0.6897	pathogenic	-0.837	Destabilizing	0.998	D	0.569	neutral	None	None	None	None	I
P/Y	0.3583	ambiguous	0.4025	ambiguous	-0.547	Destabilizing	0.991	D	0.509	neutral	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.