TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27666	83221;83222;83223	chr2:178563136;178563135;178563134	chr2:179427863;179427862;179427861
N2AB	26025	78298;78299;78300	chr2:178563136;178563135;178563134	chr2:179427863;179427862;179427861
N2A	25098	75517;75518;75519	chr2:178563136;178563135;178563134	chr2:179427863;179427862;179427861
N2B	18601	56026;56027;56028	chr2:178563136;178563135;178563134	chr2:179427863;179427862;179427861
Novex-1	18726	56401;56402;56403	chr2:178563136;178563135;178563134	chr2:179427863;179427862;179427861
Novex-2	18793	56602;56603;56604	chr2:178563136;178563135;178563134	chr2:179427863;179427862;179427861
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: Fn3-89
• Domain position: 97
• Structural Position: 130
• Q(SASA): 0.0628
• 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/G	None	None	0.376	D	0.55	0.312	0.472181857204	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
A/C	0.4665	ambiguous	0.4508	ambiguous	-2.169	Highly Destabilizing	0.977	D	0.671	prob.neutral	None	None	None	None	N
A/D	0.9764	likely_pathogenic	0.9679	pathogenic	-3.179	Highly Destabilizing	0.808	D	0.723	deleterious	D	0.525215748	None	None	N
A/E	0.9454	likely_pathogenic	0.9267	pathogenic	-3.012	Highly Destabilizing	0.848	D	0.697	prob.delet.	None	None	None	None	N
A/F	0.7969	likely_pathogenic	0.7718	pathogenic	-0.74	Destabilizing	0.848	D	0.738	deleterious	None	None	None	None	N
A/G	0.4018	ambiguous	0.3491	ambiguous	-1.598	Destabilizing	0.376	N	0.55	neutral	D	0.526229706	None	None	N
A/H	0.9674	likely_pathogenic	0.956	pathogenic	-1.506	Destabilizing	0.992	D	0.741	deleterious	None	None	None	None	N
A/I	0.2422	likely_benign	0.2361	benign	-0.355	Destabilizing	0.215	N	0.678	prob.neutral	None	None	None	None	N
A/K	0.9742	likely_pathogenic	0.9628	pathogenic	-1.373	Destabilizing	0.848	D	0.695	prob.delet.	None	None	None	None	N
A/L	0.2325	likely_benign	0.2022	benign	-0.355	Destabilizing	0.444	N	0.61	neutral	None	None	None	None	N
A/M	0.4126	ambiguous	0.3909	ambiguous	-1.071	Destabilizing	0.955	D	0.692	prob.delet.	None	None	None	None	N
A/N	0.8688	likely_pathogenic	0.8498	pathogenic	-1.899	Destabilizing	0.848	D	0.751	deleterious	None	None	None	None	N
A/P	0.1781	likely_benign	0.1633	benign	-0.623	Destabilizing	0.895	D	0.697	prob.delet.	N	0.516452509	None	None	N
A/Q	0.9077	likely_pathogenic	0.8822	pathogenic	-1.794	Destabilizing	0.848	D	0.663	prob.neutral	None	None	None	None	N
A/R	0.9376	likely_pathogenic	0.9147	pathogenic	-1.332	Destabilizing	0.848	D	0.709	prob.delet.	None	None	None	None	N
A/S	0.2231	likely_benign	0.2103	benign	-2.13	Highly Destabilizing	0.036	N	0.302	neutral	D	0.525215748	None	None	N
A/T	0.159	likely_benign	0.1552	benign	-1.865	Destabilizing	0.016	N	0.341	neutral	D	0.530168381	None	None	N
A/V	0.0992	likely_benign	0.0991	benign	-0.623	Destabilizing	0.009	N	0.325	neutral	N	0.50571544	None	None	N
A/W	0.9793	likely_pathogenic	0.9741	pathogenic	-1.298	Destabilizing	0.992	D	0.731	deleterious	None	None	None	None	N
A/Y	0.9487	likely_pathogenic	0.9349	pathogenic	-0.905	Destabilizing	0.919	D	0.739	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.