TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6218	18877;18878;18879	chr2:178729504;178729503;178729502	chr2:179594231;179594230;179594229
N2AB	5901	17926;17927;17928	chr2:178729504;178729503;178729502	chr2:179594231;179594230;179594229
N2A	4974	15145;15146;15147	chr2:178729504;178729503;178729502	chr2:179594231;179594230;179594229
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-46
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.1098
• 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/R	rs727505193	-2.071	0.999	D	0.907	0.876	None	gnomAD-2.1.1	1.43E-05	None	None	None	None	N	None	1.65453E-04	0	None	0	0	None	0	None	0	0	0
L/R	rs727505193	-2.071	0.999	D	0.907	0.876	None	gnomAD-3.1.2	4.6E-05	None	None	None	None	N	None	1.44802E-04	6.56E-05	0	0	0	None	0	0	0	0	0
L/R	rs727505193	-2.071	0.999	D	0.907	0.876	None	gnomAD-4.0.0	1.11563E-05	None	None	None	None	N	None	2.1367E-04	1.66783E-05	None	0	0	None	0	0	0	0	1.60123E-05

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	0.7656	likely_pathogenic	0.7787	pathogenic	-2.644	Highly Destabilizing	0.992	D	0.759	deleterious	None	None	None	None	N
L/C	0.8753	likely_pathogenic	0.888	pathogenic	-2.026	Highly Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
L/D	0.9968	likely_pathogenic	0.9958	pathogenic	-3.432	Highly Destabilizing	0.999	D	0.911	deleterious	None	None	None	None	N
L/E	0.9799	likely_pathogenic	0.9742	pathogenic	-3.127	Highly Destabilizing	0.999	D	0.909	deleterious	None	None	None	None	N
L/F	0.2047	likely_benign	0.215	benign	-1.615	Destabilizing	0.154	N	0.331	neutral	None	None	None	None	N
L/G	0.9594	likely_pathogenic	0.9564	pathogenic	-3.232	Highly Destabilizing	0.999	D	0.908	deleterious	None	None	None	None	N
L/H	0.9543	likely_pathogenic	0.943	pathogenic	-2.831	Highly Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
L/I	0.1487	likely_benign	0.1549	benign	-0.887	Destabilizing	0.983	D	0.613	neutral	None	None	None	None	N
L/K	0.9749	likely_pathogenic	0.9657	pathogenic	-2.179	Highly Destabilizing	0.999	D	0.907	deleterious	None	None	None	None	N
L/M	0.13	likely_benign	0.1329	benign	-1.002	Destabilizing	0.999	D	0.702	prob.neutral	D	0.551324541	None	None	N
L/N	0.9849	likely_pathogenic	0.9815	pathogenic	-2.804	Highly Destabilizing	0.999	D	0.916	deleterious	None	None	None	None	N
L/P	0.9898	likely_pathogenic	0.9852	pathogenic	-1.462	Destabilizing	0.999	D	0.915	deleterious	D	0.633792995	None	None	N
L/Q	0.9304	likely_pathogenic	0.9088	pathogenic	-2.515	Highly Destabilizing	0.999	D	0.917	deleterious	D	0.633792995	None	None	N
L/R	0.9528	likely_pathogenic	0.9384	pathogenic	-2.169	Highly Destabilizing	0.999	D	0.907	deleterious	D	0.633792995	None	None	N
L/S	0.9614	likely_pathogenic	0.958	pathogenic	-3.399	Highly Destabilizing	0.999	D	0.898	deleterious	None	None	None	None	N
L/T	0.8581	likely_pathogenic	0.8532	pathogenic	-2.928	Highly Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	N
L/V	0.1909	likely_benign	0.2022	benign	-1.462	Destabilizing	0.978	D	0.643	neutral	D	0.569867353	None	None	N
L/W	0.7282	likely_pathogenic	0.6729	pathogenic	-2.006	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
L/Y	0.7864	likely_pathogenic	0.7795	pathogenic	-1.74	Destabilizing	0.99	D	0.823	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.