TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5838	17737;17738;17739	chr2:178731153;178731152;178731151	chr2:179595880;179595879;179595878
N2AB	5521	16786;16787;16788	chr2:178731153;178731152;178731151	chr2:179595880;179595879;179595878
N2A	4594	14005;14006;14007	chr2:178731153;178731152;178731151	chr2:179595880;179595879;179595878
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: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-42
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.3726
• 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
D/A	rs772883729	-0.359	1.0	N	0.763	0.523	None	gnomAD-4.0.0	1.59154E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88281E-05	0	0	0	0
D/E	None	None	1.0	N	0.407	0.223	0.165133752707	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
D/A	0.5062	ambiguous	0.5915	pathogenic	-0.357	Destabilizing	1.0	D	0.763	deleterious	N	0.460175566	None	None	N
D/C	0.8962	likely_pathogenic	0.9471	pathogenic	0.222	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
D/E	0.3831	ambiguous	0.5167	ambiguous	-0.346	Destabilizing	1.0	D	0.407	neutral	N	0.466710682	None	None	N
D/F	0.7429	likely_pathogenic	0.8234	pathogenic	-0.509	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
D/G	0.6393	likely_pathogenic	0.7685	pathogenic	-0.541	Destabilizing	1.0	D	0.703	prob.neutral	N	0.504943783	None	None	N
D/H	0.6256	likely_pathogenic	0.676	pathogenic	-0.545	Destabilizing	1.0	D	0.729	prob.delet.	N	0.463240212	None	None	N
D/I	0.6304	likely_pathogenic	0.762	pathogenic	0.076	Stabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
D/K	0.7318	likely_pathogenic	0.7934	pathogenic	0.361	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
D/L	0.6395	likely_pathogenic	0.7455	pathogenic	0.076	Stabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
D/M	0.7875	likely_pathogenic	0.8626	pathogenic	0.409	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
D/N	0.1993	likely_benign	0.2593	benign	0.135	Stabilizing	1.0	D	0.648	neutral	N	0.50025004	None	None	N
D/P	0.9845	likely_pathogenic	0.9912	pathogenic	-0.047	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
D/Q	0.6652	likely_pathogenic	0.7334	pathogenic	0.144	Stabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
D/R	0.7888	likely_pathogenic	0.8357	pathogenic	0.358	Stabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
D/S	0.3339	likely_benign	0.4032	ambiguous	0.034	Stabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
D/T	0.6197	likely_pathogenic	0.7155	pathogenic	0.175	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
D/V	0.4922	ambiguous	0.6234	pathogenic	-0.047	Destabilizing	1.0	D	0.807	deleterious	N	0.477990332	None	None	N
D/W	0.9612	likely_pathogenic	0.973	pathogenic	-0.427	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
D/Y	0.3844	ambiguous	0.4768	ambiguous	-0.285	Destabilizing	1.0	D	0.782	deleterious	N	0.495676514	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.