TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20971	63136;63137;63138	chr2:178588814;178588813;178588812	chr2:179453541;179453540;179453539
N2AB	19330	58213;58214;58215	chr2:178588814;178588813;178588812	chr2:179453541;179453540;179453539
N2A	18403	55432;55433;55434	chr2:178588814;178588813;178588812	chr2:179453541;179453540;179453539
N2B	11906	35941;35942;35943	chr2:178588814;178588813;178588812	chr2:179453541;179453540;179453539
Novex-1	12031	36316;36317;36318	chr2:178588814;178588813;178588812	chr2:179453541;179453540;179453539
Novex-2	12098	36517;36518;36519	chr2:178588814;178588813;178588812	chr2:179453541;179453540;179453539
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: Fn3-40
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.6196
• 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	None	None	0.864	N	0.702	0.187	0.328486982098	gnomAD-4.0.0	5.47497E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.19673E-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
E/A	0.2086	likely_benign	0.1969	benign	-0.536	Destabilizing	0.645	D	0.64	neutral	N	0.516902721	None	None	N
E/C	0.8297	likely_pathogenic	0.8075	pathogenic	-0.143	Destabilizing	0.995	D	0.753	deleterious	None	None	None	None	N
E/D	0.1672	likely_benign	0.1366	benign	-0.702	Destabilizing	0.002	N	0.248	neutral	D	0.523540692	None	None	N
E/F	0.7573	likely_pathogenic	0.7111	pathogenic	-0.285	Destabilizing	0.995	D	0.729	prob.delet.	None	None	None	None	N
E/G	0.4036	ambiguous	0.3711	ambiguous	-0.804	Destabilizing	0.645	D	0.637	neutral	N	0.510150107	None	None	N
E/H	0.532	ambiguous	0.4805	ambiguous	-0.393	Destabilizing	0.985	D	0.701	prob.neutral	None	None	None	None	N
E/I	0.2577	likely_benign	0.232	benign	0.162	Stabilizing	0.945	D	0.743	deleterious	None	None	None	None	N
E/K	0.2436	likely_benign	0.2272	benign	0.024	Stabilizing	0.645	D	0.589	neutral	N	0.486905101	None	None	N
E/L	0.3815	ambiguous	0.351	ambiguous	0.162	Stabilizing	0.945	D	0.741	deleterious	None	None	None	None	N
E/M	0.4256	ambiguous	0.3967	ambiguous	0.38	Stabilizing	0.995	D	0.745	deleterious	None	None	None	None	N
E/N	0.3288	likely_benign	0.2808	benign	-0.347	Destabilizing	0.809	D	0.71	prob.delet.	None	None	None	None	N
E/P	0.9657	likely_pathogenic	0.9472	pathogenic	-0.049	Destabilizing	0.945	D	0.768	deleterious	None	None	None	None	N
E/Q	0.1635	likely_benign	0.1644	benign	-0.29	Destabilizing	0.864	D	0.702	prob.neutral	N	0.473669232	None	None	N
E/R	0.3749	ambiguous	0.3336	benign	0.193	Stabilizing	0.894	D	0.717	prob.delet.	None	None	None	None	N
E/S	0.2599	likely_benign	0.2375	benign	-0.535	Destabilizing	0.547	D	0.596	neutral	None	None	None	None	N
E/T	0.2257	likely_benign	0.2118	benign	-0.319	Destabilizing	0.894	D	0.733	prob.delet.	None	None	None	None	N
E/V	0.1557	likely_benign	0.149	benign	-0.049	Destabilizing	0.928	D	0.741	deleterious	N	0.502453344	None	None	N
E/W	0.9161	likely_pathogenic	0.8945	pathogenic	-0.096	Destabilizing	0.995	D	0.754	deleterious	None	None	None	None	N
E/Y	0.6545	likely_pathogenic	0.5956	pathogenic	-0.034	Destabilizing	0.995	D	0.749	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.