TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33141	99646;99647;99648	chr2:178537786;178537785;178537784	chr2:179402513;179402512;179402511
N2AB	31500	94723;94724;94725	chr2:178537786;178537785;178537784	chr2:179402513;179402512;179402511
N2A	30573	91942;91943;91944	chr2:178537786;178537785;178537784	chr2:179402513;179402512;179402511
N2B	24076	72451;72452;72453	chr2:178537786;178537785;178537784	chr2:179402513;179402512;179402511
Novex-1	24201	72826;72827;72828	chr2:178537786;178537785;178537784	chr2:179402513;179402512;179402511
Novex-2	24268	73027;73028;73029	chr2:178537786;178537785;178537784	chr2:179402513;179402512;179402511
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-156
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.1445
• 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
L/F	rs886039134	None	0.999	N	0.76	0.433	0.734641109744	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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
L/A	0.9501	likely_pathogenic	0.9523	pathogenic	-2.25	Highly Destabilizing	0.999	D	0.557	neutral	None	None	None	None	N
L/C	0.9562	likely_pathogenic	0.9627	pathogenic	-1.268	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
L/D	0.9994	likely_pathogenic	0.9994	pathogenic	-2.74	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
L/E	0.9939	likely_pathogenic	0.9945	pathogenic	-2.487	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/F	0.8693	likely_pathogenic	0.9044	pathogenic	-1.445	Destabilizing	0.999	D	0.76	deleterious	N	0.51265256	None	None	N
L/G	0.9943	likely_pathogenic	0.9947	pathogenic	-2.761	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/H	0.9917	likely_pathogenic	0.9931	pathogenic	-2.192	Highly Destabilizing	1.0	D	0.85	deleterious	D	0.526484693	None	None	N
L/I	0.1396	likely_benign	0.1575	benign	-0.754	Destabilizing	0.882	D	0.532	neutral	N	0.430012534	None	None	N
L/K	0.9898	likely_pathogenic	0.9902	pathogenic	-1.682	Destabilizing	0.998	D	0.817	deleterious	None	None	None	None	N
L/M	0.3722	ambiguous	0.406	ambiguous	-0.609	Destabilizing	0.998	D	0.787	deleterious	None	None	None	None	N
L/N	0.9944	likely_pathogenic	0.9935	pathogenic	-2.16	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
L/P	0.9963	likely_pathogenic	0.9964	pathogenic	-1.239	Destabilizing	1.0	D	0.871	deleterious	N	0.500720663	None	None	N
L/Q	0.9813	likely_pathogenic	0.9848	pathogenic	-1.982	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
L/R	0.9841	likely_pathogenic	0.9864	pathogenic	-1.536	Destabilizing	1.0	D	0.863	deleterious	N	0.521458264	None	None	N
L/S	0.9955	likely_pathogenic	0.9959	pathogenic	-2.754	Highly Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
L/T	0.962	likely_pathogenic	0.9635	pathogenic	-2.355	Highly Destabilizing	0.999	D	0.746	deleterious	None	None	None	None	N
L/V	0.2201	likely_benign	0.2535	benign	-1.239	Destabilizing	0.209	N	0.433	neutral	N	0.471803229	None	None	N
L/W	0.9844	likely_pathogenic	0.9893	pathogenic	-1.817	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
L/Y	0.9857	likely_pathogenic	0.9881	pathogenic	-1.47	Destabilizing	0.999	D	0.851	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.