TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5796	17611;17612;17613	chr2:178731380;178731379;178731378	chr2:179596107;179596106;179596105
N2AB	5479	16660;16661;16662	chr2:178731380;178731379;178731378	chr2:179596107;179596106;179596105
N2A	4552	13879;13880;13881	chr2:178731380;178731379;178731378	chr2:179596107;179596106;179596105
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: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-41
• Domain position: 67
• Structural Position: 149
• Q(SASA): 0.1183
• 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
H/D	rs397517485	-2.267	0.995	N	0.805	0.439	0.21737058555	gnomAD-2.1.1	3.62E-05	None	None	None	None	N	None	0	0	None	0	0	None	2.94118E-04	None	0	0	0
H/D	rs397517485	-2.267	0.995	N	0.805	0.439	0.21737058555	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07814E-04	0
H/D	rs397517485	-2.267	0.995	N	0.805	0.439	0.21737058555	gnomAD-4.0.0	1.17749E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.0864E-04	0
H/Y	None	None	0.982	N	0.701	0.43	0.423597194605	gnomAD-4.0.0	6.84206E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99475E-07	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
H/A	0.6485	likely_pathogenic	0.6556	pathogenic	-1.769	Destabilizing	0.919	D	0.783	deleterious	None	None	None	None	N
H/C	0.5448	ambiguous	0.5491	ambiguous	-0.898	Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	N
H/D	0.1611	likely_benign	0.1604	benign	-1.704	Destabilizing	0.995	D	0.805	deleterious	N	0.42197847	None	None	N
H/E	0.5914	likely_pathogenic	0.6037	pathogenic	-1.522	Destabilizing	0.986	D	0.702	prob.neutral	None	None	None	None	N
H/F	0.6697	likely_pathogenic	0.6663	pathogenic	0.053	Stabilizing	0.976	D	0.793	deleterious	None	None	None	None	N
H/G	0.6542	likely_pathogenic	0.6548	pathogenic	-2.205	Highly Destabilizing	0.986	D	0.833	deleterious	None	None	None	None	N
H/I	0.7355	likely_pathogenic	0.75	pathogenic	-0.489	Destabilizing	0.952	D	0.846	deleterious	None	None	None	None	N
H/K	0.7592	likely_pathogenic	0.7796	pathogenic	-1.3	Destabilizing	0.988	D	0.808	deleterious	None	None	None	None	N
H/L	0.3409	ambiguous	0.3571	ambiguous	-0.489	Destabilizing	0.026	N	0.648	neutral	N	0.485034447	None	None	N
H/M	0.6616	likely_pathogenic	0.6707	pathogenic	-0.647	Destabilizing	0.976	D	0.842	deleterious	None	None	None	None	N
H/N	0.0921	likely_benign	0.0986	benign	-1.907	Destabilizing	0.982	D	0.693	prob.neutral	N	0.51010254	None	None	N
H/P	0.7384	likely_pathogenic	0.6978	pathogenic	-0.904	Destabilizing	0.995	D	0.847	deleterious	N	0.507822736	None	None	N
H/Q	0.3883	ambiguous	0.4256	ambiguous	-1.541	Destabilizing	0.995	D	0.719	prob.delet.	D	0.529555092	None	None	N
H/R	0.5929	likely_pathogenic	0.6274	pathogenic	-1.743	Destabilizing	0.984	D	0.739	prob.delet.	N	0.496301847	None	None	N
H/S	0.4088	ambiguous	0.415	ambiguous	-1.958	Destabilizing	0.959	D	0.8	deleterious	None	None	None	None	N
H/T	0.5671	likely_pathogenic	0.5964	pathogenic	-1.643	Destabilizing	0.988	D	0.835	deleterious	None	None	None	None	N
H/V	0.678	likely_pathogenic	0.7122	pathogenic	-0.904	Destabilizing	0.851	D	0.821	deleterious	None	None	None	None	N
H/W	0.7294	likely_pathogenic	0.7241	pathogenic	0.643	Stabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
H/Y	0.2177	likely_benign	0.2262	benign	0.413	Stabilizing	0.982	D	0.701	prob.neutral	N	0.496301847	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.