TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24070	72433;72434;72435	chr2:178573924;178573923;178573922	chr2:179438651;179438650;179438649
N2AB	22429	67510;67511;67512	chr2:178573924;178573923;178573922	chr2:179438651;179438650;179438649
N2A	21502	64729;64730;64731	chr2:178573924;178573923;178573922	chr2:179438651;179438650;179438649
N2B	15005	45238;45239;45240	chr2:178573924;178573923;178573922	chr2:179438651;179438650;179438649
Novex-1	15130	45613;45614;45615	chr2:178573924;178573923;178573922	chr2:179438651;179438650;179438649
Novex-2	15197	45814;45815;45816	chr2:178573924;178573923;178573922	chr2:179438651;179438650;179438649
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-131
• Domain position: 42
• Structural Position: 58
• Q(SASA): 0.2168
• 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/Q	rs1709142629	None	0.996	D	0.818	0.682	0.798245613507	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
L/Q	rs1709142629	None	0.996	D	0.818	0.682	0.798245613507	gnomAD-4.0.0	6.57272E-06	None	None	None	None	N	None	0	6.54536E-05	None	0	0	None	0	0	0	0	0
L/V	None	None	0.039	N	0.381	0.147	0.414021929199	gnomAD-4.0.0	6.84521E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9973E-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
L/A	0.4521	ambiguous	0.4991	ambiguous	-1.926	Destabilizing	0.895	D	0.542	neutral	None	None	None	None	N
L/C	0.698	likely_pathogenic	0.7319	pathogenic	-1.526	Destabilizing	0.998	D	0.756	deleterious	None	None	None	None	N
L/D	0.9579	likely_pathogenic	0.9645	pathogenic	-1.0	Destabilizing	0.997	D	0.825	deleterious	None	None	None	None	N
L/E	0.7992	likely_pathogenic	0.8189	pathogenic	-0.865	Destabilizing	0.992	D	0.818	deleterious	None	None	None	None	N
L/F	0.2752	likely_benign	0.3186	benign	-1.096	Destabilizing	0.983	D	0.749	deleterious	None	None	None	None	N
L/G	0.8489	likely_pathogenic	0.8626	pathogenic	-2.352	Highly Destabilizing	0.992	D	0.81	deleterious	None	None	None	None	N
L/H	0.7133	likely_pathogenic	0.7443	pathogenic	-1.311	Destabilizing	0.999	D	0.822	deleterious	None	None	None	None	N
L/I	0.0814	likely_benign	0.0852	benign	-0.764	Destabilizing	0.745	D	0.503	neutral	None	None	None	None	N
L/K	0.7361	likely_pathogenic	0.7487	pathogenic	-1.313	Destabilizing	0.992	D	0.793	deleterious	None	None	None	None	N
L/M	0.1434	likely_benign	0.1488	benign	-0.894	Destabilizing	0.978	D	0.769	deleterious	N	0.505137981	None	None	N
L/N	0.8549	likely_pathogenic	0.8609	pathogenic	-1.454	Destabilizing	0.997	D	0.823	deleterious	None	None	None	None	N
L/P	0.7961	likely_pathogenic	0.8076	pathogenic	-1.125	Destabilizing	0.996	D	0.827	deleterious	D	0.538245846	None	None	N
L/Q	0.5838	likely_pathogenic	0.6128	pathogenic	-1.386	Destabilizing	0.996	D	0.818	deleterious	D	0.534878484	None	None	N
L/R	0.6545	likely_pathogenic	0.6811	pathogenic	-0.955	Destabilizing	0.989	D	0.821	deleterious	N	0.521622848	None	None	N
L/S	0.7416	likely_pathogenic	0.788	pathogenic	-2.231	Highly Destabilizing	0.983	D	0.797	deleterious	None	None	None	None	N
L/T	0.3985	ambiguous	0.4419	ambiguous	-1.938	Destabilizing	0.983	D	0.733	prob.delet.	None	None	None	None	N
L/V	0.0969	likely_benign	0.1076	benign	-1.125	Destabilizing	0.039	N	0.381	neutral	N	0.503318214	None	None	N
L/W	0.5385	ambiguous	0.5986	pathogenic	-1.145	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
L/Y	0.6663	likely_pathogenic	0.7038	pathogenic	-0.937	Destabilizing	0.992	D	0.817	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.