TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29980	90163;90164;90165	chr2:178552962;178552961;178552960	chr2:179417689;179417688;179417687
N2AB	28339	85240;85241;85242	chr2:178552962;178552961;178552960	chr2:179417689;179417688;179417687
N2A	27412	82459;82460;82461	chr2:178552962;178552961;178552960	chr2:179417689;179417688;179417687
N2B	20915	62968;62969;62970	chr2:178552962;178552961;178552960	chr2:179417689;179417688;179417687
Novex-1	21040	63343;63344;63345	chr2:178552962;178552961;178552960	chr2:179417689;179417688;179417687
Novex-2	21107	63544;63545;63546	chr2:178552962;178552961;178552960	chr2:179417689;179417688;179417687
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Fn3-106
• Domain position: 48
• Structural Position: 65
• Q(SASA): 0.2467
• 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
W/R	None	None	0.988	D	0.509	0.498	0.729369889639	gnomAD-4.0.0	6.84488E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99437E-07	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
W/A	0.978	likely_pathogenic	0.9601	pathogenic	-3.155	Highly Destabilizing	0.969	D	0.449	neutral	None	None	None	None	N
W/C	0.9889	likely_pathogenic	0.9764	pathogenic	-1.442	Destabilizing	0.999	D	0.461	neutral	N	0.519071731	None	None	N
W/D	0.9968	likely_pathogenic	0.9937	pathogenic	-1.744	Destabilizing	0.997	D	0.501	neutral	None	None	None	None	N
W/E	0.998	likely_pathogenic	0.9958	pathogenic	-1.675	Destabilizing	0.997	D	0.471	neutral	None	None	None	None	N
W/F	0.4218	ambiguous	0.3813	ambiguous	-2.017	Highly Destabilizing	0.046	N	0.105	neutral	None	None	None	None	N
W/G	0.9432	likely_pathogenic	0.9055	pathogenic	-3.344	Highly Destabilizing	0.986	D	0.408	neutral	D	0.529832152	None	None	N
W/H	0.9808	likely_pathogenic	0.9637	pathogenic	-1.569	Destabilizing	0.982	D	0.482	neutral	None	None	None	None	N
W/I	0.9806	likely_pathogenic	0.9654	pathogenic	-2.466	Highly Destabilizing	0.939	D	0.464	neutral	None	None	None	None	N
W/K	0.9984	likely_pathogenic	0.9963	pathogenic	-1.57	Destabilizing	0.991	D	0.467	neutral	None	None	None	None	N
W/L	0.9349	likely_pathogenic	0.8861	pathogenic	-2.466	Highly Destabilizing	0.704	D	0.441	neutral	D	0.527804236	None	None	N
W/M	0.9842	likely_pathogenic	0.9719	pathogenic	-1.925	Destabilizing	0.997	D	0.395	neutral	None	None	None	None	N
W/N	0.9925	likely_pathogenic	0.9861	pathogenic	-1.84	Destabilizing	0.997	D	0.503	neutral	None	None	None	None	N
W/P	0.9923	likely_pathogenic	0.9863	pathogenic	-2.712	Highly Destabilizing	0.997	D	0.497	neutral	None	None	None	None	N
W/Q	0.998	likely_pathogenic	0.9954	pathogenic	-1.909	Destabilizing	0.997	D	0.489	neutral	None	None	None	None	N
W/R	0.9956	likely_pathogenic	0.9902	pathogenic	-0.884	Destabilizing	0.988	D	0.509	neutral	D	0.540934968	None	None	N
W/S	0.9566	likely_pathogenic	0.9217	pathogenic	-2.35	Highly Destabilizing	0.988	D	0.462	neutral	D	0.529071683	None	None	N
W/T	0.9851	likely_pathogenic	0.9705	pathogenic	-2.236	Highly Destabilizing	0.969	D	0.423	neutral	None	None	None	None	N
W/V	0.97	likely_pathogenic	0.9458	pathogenic	-2.712	Highly Destabilizing	0.939	D	0.432	neutral	None	None	None	None	N
W/Y	0.5354	ambiguous	0.4783	ambiguous	-1.737	Destabilizing	0.079	N	0.091	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.