TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24484	73675;73676;73677	chr2:178572682;178572681;178572680	chr2:179437409;179437408;179437407
N2AB	22843	68752;68753;68754	chr2:178572682;178572681;178572680	chr2:179437409;179437408;179437407
N2A	21916	65971;65972;65973	chr2:178572682;178572681;178572680	chr2:179437409;179437408;179437407
N2B	15419	46480;46481;46482	chr2:178572682;178572681;178572680	chr2:179437409;179437408;179437407
Novex-1	15544	46855;46856;46857	chr2:178572682;178572681;178572680	chr2:179437409;179437408;179437407
Novex-2	15611	47056;47057;47058	chr2:178572682;178572681;178572680	chr2:179437409;179437408;179437407
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-132
• Domain position: 54
• Structural Position: 138
• Q(SASA): 0.1181
• 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/P	None	None	0.998	D	0.891	0.83	0.831601111556	gnomAD-4.0.0	1.59241E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86049E-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	0.9353	likely_pathogenic	0.9291	pathogenic	-2.53	Highly Destabilizing	0.938	D	0.692	prob.neutral	None	None	None	None	N
L/C	0.8734	likely_pathogenic	0.8647	pathogenic	-1.686	Destabilizing	0.334	N	0.608	neutral	None	None	None	None	N
L/D	0.9997	likely_pathogenic	0.9996	pathogenic	-3.252	Highly Destabilizing	0.998	D	0.892	deleterious	None	None	None	None	N
L/E	0.9976	likely_pathogenic	0.9968	pathogenic	-2.913	Highly Destabilizing	0.998	D	0.873	deleterious	None	None	None	None	N
L/F	0.5822	likely_pathogenic	0.6044	pathogenic	-1.53	Destabilizing	0.994	D	0.797	deleterious	N	0.507050539	None	None	N
L/G	0.9911	likely_pathogenic	0.9892	pathogenic	-3.149	Highly Destabilizing	0.995	D	0.881	deleterious	None	None	None	None	N
L/H	0.9854	likely_pathogenic	0.9827	pathogenic	-2.976	Highly Destabilizing	0.999	D	0.871	deleterious	D	0.563884972	None	None	N
L/I	0.3173	likely_benign	0.3213	benign	-0.659	Destabilizing	0.958	D	0.675	neutral	N	0.515253292	None	None	N
L/K	0.993	likely_pathogenic	0.9913	pathogenic	-1.992	Destabilizing	0.995	D	0.859	deleterious	None	None	None	None	N
L/M	0.3004	likely_benign	0.299	benign	-0.821	Destabilizing	0.998	D	0.78	deleterious	None	None	None	None	N
L/N	0.9975	likely_pathogenic	0.9966	pathogenic	-2.782	Highly Destabilizing	0.998	D	0.892	deleterious	None	None	None	None	N
L/P	0.9983	likely_pathogenic	0.9979	pathogenic	-1.275	Destabilizing	0.998	D	0.891	deleterious	D	0.563884972	None	None	N
L/Q	0.9787	likely_pathogenic	0.974	pathogenic	-2.348	Highly Destabilizing	0.998	D	0.864	deleterious	None	None	None	None	N
L/R	0.9838	likely_pathogenic	0.9816	pathogenic	-2.23	Highly Destabilizing	0.998	D	0.862	deleterious	D	0.563884972	None	None	N
L/S	0.9939	likely_pathogenic	0.9923	pathogenic	-3.29	Highly Destabilizing	0.991	D	0.855	deleterious	None	None	None	None	N
L/T	0.9854	likely_pathogenic	0.9818	pathogenic	-2.774	Highly Destabilizing	0.991	D	0.78	deleterious	None	None	None	None	N
L/V	0.3224	likely_benign	0.3347	benign	-1.275	Destabilizing	0.958	D	0.695	prob.neutral	D	0.535777084	None	None	N
L/W	0.9564	likely_pathogenic	0.9488	pathogenic	-1.904	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
L/Y	0.9465	likely_pathogenic	0.9457	pathogenic	-1.691	Destabilizing	0.998	D	0.791	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.