TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27679	83260;83261;83262	chr2:178563097;178563096;178563095	chr2:179427824;179427823;179427822
N2AB	26038	78337;78338;78339	chr2:178563097;178563096;178563095	chr2:179427824;179427823;179427822
N2A	25111	75556;75557;75558	chr2:178563097;178563096;178563095	chr2:179427824;179427823;179427822
N2B	18614	56065;56066;56067	chr2:178563097;178563096;178563095	chr2:179427824;179427823;179427822
Novex-1	18739	56440;56441;56442	chr2:178563097;178563096;178563095	chr2:179427824;179427823;179427822
Novex-2	18806	56641;56642;56643	chr2:178563097;178563096;178563095	chr2:179427824;179427823;179427822
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: Ig-141
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.3565
• 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/T	rs1704286522	None	0.999	N	0.707	0.278	0.308278614506	gnomAD-4.0.0	1.59137E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85873E-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	0.7643	likely_pathogenic	0.7476	pathogenic	-0.63	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
A/D	0.8759	likely_pathogenic	0.8317	pathogenic	-0.601	Destabilizing	0.999	D	0.748	deleterious	D	0.530304454	None	None	N
A/E	0.8492	likely_pathogenic	0.7753	pathogenic	-0.759	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
A/F	0.7536	likely_pathogenic	0.729	pathogenic	-0.911	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
A/G	0.3041	likely_benign	0.2848	benign	-0.349	Destabilizing	0.434	N	0.371	neutral	N	0.513988207	None	None	N
A/H	0.8643	likely_pathogenic	0.8251	pathogenic	-0.433	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
A/I	0.5548	ambiguous	0.5185	ambiguous	-0.316	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
A/K	0.9236	likely_pathogenic	0.8705	pathogenic	-0.706	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
A/L	0.4103	ambiguous	0.3663	ambiguous	-0.316	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
A/M	0.4606	ambiguous	0.4171	ambiguous	-0.295	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
A/N	0.6305	likely_pathogenic	0.5758	pathogenic	-0.289	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
A/P	0.4877	ambiguous	0.4419	ambiguous	-0.272	Destabilizing	1.0	D	0.769	deleterious	N	0.48670306	None	None	N
A/Q	0.7538	likely_pathogenic	0.6756	pathogenic	-0.594	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
A/R	0.866	likely_pathogenic	0.8008	pathogenic	-0.205	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
A/S	0.1647	likely_benign	0.154	benign	-0.471	Destabilizing	0.996	D	0.588	neutral	N	0.51102526	None	None	N
A/T	0.2126	likely_benign	0.1952	benign	-0.555	Destabilizing	0.999	D	0.707	prob.neutral	N	0.481966119	None	None	N
A/V	0.2733	likely_benign	0.2535	benign	-0.272	Destabilizing	0.999	D	0.68	prob.neutral	N	0.510158468	None	None	N
A/W	0.9527	likely_pathogenic	0.9393	pathogenic	-1.069	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
A/Y	0.8533	likely_pathogenic	0.8237	pathogenic	-0.718	Destabilizing	1.0	D	0.763	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.