TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31347	94264;94265;94266	chr2:178547587;178547586;178547585	chr2:179412314;179412313;179412312
N2AB	29706	89341;89342;89343	chr2:178547587;178547586;178547585	chr2:179412314;179412313;179412312
N2A	28779	86560;86561;86562	chr2:178547587;178547586;178547585	chr2:179412314;179412313;179412312
N2B	22282	67069;67070;67071	chr2:178547587;178547586;178547585	chr2:179412314;179412313;179412312
Novex-1	22407	67444;67445;67446	chr2:178547587;178547586;178547585	chr2:179412314;179412313;179412312
Novex-2	22474	67645;67646;67647	chr2:178547587;178547586;178547585	chr2:179412314;179412313;179412312
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-116
• Domain position: 40
• Structural Position: 41
• Q(SASA): 0.1001
• 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
E/Q	rs886055230	None	1.0	N	0.779	0.287	0.270001397563	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.93125E-04	None	0	0	0	0	0
E/Q	rs886055230	None	1.0	N	0.779	0.287	0.270001397563	gnomAD-4.0.0	1.79338E-05	None	None	None	None	N	None	0	0	None	0	3.39526E-04	None	0	0	0	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
E/A	0.8896	likely_pathogenic	0.9084	pathogenic	-1.756	Destabilizing	0.999	D	0.738	prob.delet.	D	0.533051837	None	None	N
E/C	0.9801	likely_pathogenic	0.9822	pathogenic	-0.784	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
E/D	0.9067	likely_pathogenic	0.9173	pathogenic	-1.666	Destabilizing	0.999	D	0.681	prob.neutral	N	0.475207126	None	None	N
E/F	0.9884	likely_pathogenic	0.9912	pathogenic	-1.402	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
E/G	0.9172	likely_pathogenic	0.9293	pathogenic	-2.142	Highly Destabilizing	1.0	D	0.785	deleterious	N	0.511949069	None	None	N
E/H	0.9543	likely_pathogenic	0.9592	pathogenic	-1.186	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/I	0.9808	likely_pathogenic	0.9853	pathogenic	-0.64	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
E/K	0.9093	likely_pathogenic	0.9252	pathogenic	-1.489	Destabilizing	0.999	D	0.69	prob.neutral	N	0.520428084	None	None	N
E/L	0.9401	likely_pathogenic	0.956	pathogenic	-0.64	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
E/M	0.9452	likely_pathogenic	0.9577	pathogenic	0.119	Stabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
E/N	0.9781	likely_pathogenic	0.9809	pathogenic	-1.683	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/P	0.9999	likely_pathogenic	0.9998	pathogenic	-1.0	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
E/Q	0.4955	ambiguous	0.5187	ambiguous	-1.431	Destabilizing	1.0	D	0.779	deleterious	N	0.501991984	None	None	N
E/R	0.936	likely_pathogenic	0.9414	pathogenic	-1.271	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
E/S	0.9092	likely_pathogenic	0.9198	pathogenic	-2.359	Highly Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
E/T	0.9656	likely_pathogenic	0.9685	pathogenic	-1.988	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
E/V	0.9466	likely_pathogenic	0.9578	pathogenic	-1.0	Destabilizing	1.0	D	0.785	deleterious	N	0.51093511	None	None	N
E/W	0.9918	likely_pathogenic	0.9933	pathogenic	-1.389	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
E/Y	0.9772	likely_pathogenic	0.9832	pathogenic	-1.17	Destabilizing	1.0	D	0.843	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.