TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9040	27343;27344;27345	chr2:178712907;178712906;178712905	chr2:179577634;179577633;179577632
N2AB	8723	26392;26393;26394	chr2:178712907;178712906;178712905	chr2:179577634;179577633;179577632
N2A	7796	23611;23612;23613	chr2:178712907;178712906;178712905	chr2:179577634;179577633;179577632
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: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-76
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.1746
• 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
S/G	rs751149532	-1.346	0.27	N	0.605	0.183	0.146414634003	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
S/G	rs751149532	-1.346	0.27	N	0.605	0.183	0.146414634003	gnomAD-4.0.0	1.5926E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02608E-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
S/A	0.0736	likely_benign	0.0752	benign	-0.728	Destabilizing	0.003	N	0.293	neutral	None	None	None	None	N
S/C	0.1083	likely_benign	0.1134	benign	-0.503	Destabilizing	0.013	N	0.599	neutral	N	0.331897105	None	None	N
S/D	0.9712	likely_pathogenic	0.979	pathogenic	-1.643	Destabilizing	0.828	D	0.639	neutral	None	None	None	None	N
S/E	0.9842	likely_pathogenic	0.9898	pathogenic	-1.413	Destabilizing	0.704	D	0.622	neutral	None	None	None	None	N
S/F	0.7583	likely_pathogenic	0.8246	pathogenic	-0.449	Destabilizing	0.893	D	0.804	deleterious	None	None	None	None	N
S/G	0.1465	likely_benign	0.16	benign	-1.146	Destabilizing	0.27	N	0.605	neutral	N	0.452013376	None	None	N
S/H	0.9548	likely_pathogenic	0.9666	pathogenic	-1.487	Destabilizing	0.981	D	0.773	deleterious	None	None	None	None	N
S/I	0.5006	ambiguous	0.5596	ambiguous	0.35	Stabilizing	0.473	N	0.751	deleterious	N	0.492915849	None	None	N
S/K	0.997	likely_pathogenic	0.9982	pathogenic	-0.232	Destabilizing	0.031	N	0.389	neutral	None	None	None	None	N
S/L	0.2704	likely_benign	0.3205	benign	0.35	Stabilizing	0.329	N	0.711	prob.delet.	None	None	None	None	N
S/M	0.4684	ambiguous	0.5116	ambiguous	0.138	Stabilizing	0.176	N	0.637	neutral	None	None	None	None	N
S/N	0.7415	likely_pathogenic	0.7827	pathogenic	-1.061	Destabilizing	0.784	D	0.653	neutral	N	0.453019088	None	None	N
S/P	0.9389	likely_pathogenic	0.9647	pathogenic	0.025	Stabilizing	0.944	D	0.765	deleterious	None	None	None	None	N
S/Q	0.9749	likely_pathogenic	0.9825	pathogenic	-0.69	Destabilizing	0.893	D	0.696	prob.neutral	None	None	None	None	N
S/R	0.992	likely_pathogenic	0.9951	pathogenic	-0.731	Destabilizing	0.473	N	0.731	prob.delet.	N	0.453019088	None	None	N
S/T	0.1535	likely_benign	0.1522	benign	-0.635	Destabilizing	0.425	N	0.577	neutral	N	0.5076933	None	None	N
S/V	0.3403	ambiguous	0.3677	ambiguous	0.025	Stabilizing	0.329	N	0.722	prob.delet.	None	None	None	None	N
S/W	0.9162	likely_pathogenic	0.9474	pathogenic	-0.848	Destabilizing	0.995	D	0.826	deleterious	None	None	None	None	N
S/Y	0.7986	likely_pathogenic	0.8591	pathogenic	-0.345	Destabilizing	0.981	D	0.809	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.