TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21796	65611;65612;65613	chr2:178583796;178583795;178583794	chr2:179448523;179448522;179448521
N2AB	20155	60688;60689;60690	chr2:178583796;178583795;178583794	chr2:179448523;179448522;179448521
N2A	19228	57907;57908;57909	chr2:178583796;178583795;178583794	chr2:179448523;179448522;179448521
N2B	12731	38416;38417;38418	chr2:178583796;178583795;178583794	chr2:179448523;179448522;179448521
Novex-1	12856	38791;38792;38793	chr2:178583796;178583795;178583794	chr2:179448523;179448522;179448521
Novex-2	12923	38992;38993;38994	chr2:178583796;178583795;178583794	chr2:179448523;179448522;179448521
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-46
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.0835
• 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
A/V	rs752002587	0.211	0.669	N	0.635	0.223	0.446111551642	gnomAD-2.1.1	4.12E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.12E-06	0
A/V	rs752002587	0.211	0.669	N	0.635	0.223	0.446111551642	gnomAD-4.0.0	1.60002E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87143E-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
A/C	0.3915	ambiguous	0.3893	ambiguous	-0.299	Destabilizing	0.998	D	0.758	deleterious	None	None	None	None	N
A/D	0.8569	likely_pathogenic	0.8247	pathogenic	-2.051	Highly Destabilizing	0.934	D	0.839	deleterious	N	0.48685292	None	None	N
A/E	0.6311	likely_pathogenic	0.6058	pathogenic	-1.802	Destabilizing	0.842	D	0.795	deleterious	None	None	None	None	N
A/F	0.2932	likely_benign	0.2549	benign	-0.346	Destabilizing	0.016	N	0.703	prob.neutral	None	None	None	None	N
A/G	0.2225	likely_benign	0.2117	benign	-1.12	Destabilizing	0.669	D	0.673	neutral	N	0.499645112	None	None	N
A/H	0.6105	likely_pathogenic	0.5808	pathogenic	-1.865	Destabilizing	0.949	D	0.841	deleterious	None	None	None	None	N
A/I	0.3187	likely_benign	0.2635	benign	0.742	Stabilizing	0.728	D	0.773	deleterious	None	None	None	None	N
A/K	0.6976	likely_pathogenic	0.6681	pathogenic	-0.533	Destabilizing	0.842	D	0.787	deleterious	None	None	None	None	N
A/L	0.2849	likely_benign	0.2532	benign	0.742	Stabilizing	0.525	D	0.737	prob.delet.	None	None	None	None	N
A/M	0.248	likely_benign	0.2158	benign	0.486	Stabilizing	0.325	N	0.662	neutral	None	None	None	None	N
A/N	0.6196	likely_pathogenic	0.5695	pathogenic	-0.97	Destabilizing	0.949	D	0.839	deleterious	None	None	None	None	N
A/P	0.9899	likely_pathogenic	0.9877	pathogenic	0.327	Stabilizing	0.966	D	0.847	deleterious	N	0.48685292	None	None	N
A/Q	0.4872	ambiguous	0.4762	ambiguous	-0.66	Destabilizing	0.974	D	0.848	deleterious	None	None	None	None	N
A/R	0.5999	likely_pathogenic	0.586	pathogenic	-0.921	Destabilizing	0.949	D	0.842	deleterious	None	None	None	None	N
A/S	0.1375	likely_benign	0.1254	benign	-1.283	Destabilizing	0.051	N	0.386	neutral	N	0.491582989	None	None	N
A/T	0.1511	likely_benign	0.1247	benign	-0.91	Destabilizing	0.669	D	0.725	prob.delet.	N	0.502010626	None	None	N
A/V	0.1633	likely_benign	0.1391	benign	0.327	Stabilizing	0.669	D	0.635	neutral	N	0.487521177	None	None	N
A/W	0.7885	likely_pathogenic	0.7642	pathogenic	-1.295	Destabilizing	0.998	D	0.832	deleterious	None	None	None	None	N
A/Y	0.393	ambiguous	0.373	ambiguous	-0.621	Destabilizing	0.067	N	0.583	neutral	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.