TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23519	70780;70781;70782	chr2:178575577;178575576;178575575	chr2:179440304;179440303;179440302
N2AB	21878	65857;65858;65859	chr2:178575577;178575576;178575575	chr2:179440304;179440303;179440302
N2A	20951	63076;63077;63078	chr2:178575577;178575576;178575575	chr2:179440304;179440303;179440302
N2B	14454	43585;43586;43587	chr2:178575577;178575576;178575575	chr2:179440304;179440303;179440302
Novex-1	14579	43960;43961;43962	chr2:178575577;178575576;178575575	chr2:179440304;179440303;179440302
Novex-2	14646	44161;44162;44163	chr2:178575577;178575576;178575575	chr2:179440304;179440303;179440302
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-58
• Domain position: 85
• Structural Position: 119
• Q(SASA): 0.5534
• Predicted PPI site: I

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
E/K	rs1267057579	0.57	0.822	N	0.637	0.245	0.371344866733	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
E/K	rs1267057579	0.57	0.822	N	0.637	0.245	0.371344866733	gnomAD-4.0.0	2.05277E-06	None	None	None	None	I	None	0	0	None	0	2.51978E-05	None	0	0	1.7991E-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
E/A	0.2347	likely_benign	0.278	benign	-0.477	Destabilizing	0.698	D	0.647	neutral	N	0.469887527	None	None	I
E/C	0.8588	likely_pathogenic	0.8844	pathogenic	-0.047	Destabilizing	0.998	D	0.763	deleterious	None	None	None	None	I
E/D	0.2082	likely_benign	0.2245	benign	-0.441	Destabilizing	0.904	D	0.603	neutral	N	0.493527216	None	None	I
E/F	0.7492	likely_pathogenic	0.8251	pathogenic	-0.399	Destabilizing	0.956	D	0.74	deleterious	None	None	None	None	I
E/G	0.4182	ambiguous	0.4919	ambiguous	-0.679	Destabilizing	0.822	D	0.666	neutral	N	0.481888943	None	None	I
E/H	0.6764	likely_pathogenic	0.7467	pathogenic	-0.245	Destabilizing	0.998	D	0.577	neutral	None	None	None	None	I
E/I	0.2033	likely_benign	0.2661	benign	0.022	Stabilizing	0.754	D	0.687	prob.neutral	None	None	None	None	I
E/K	0.2745	likely_benign	0.3644	ambiguous	0.211	Stabilizing	0.822	D	0.637	neutral	N	0.509438031	None	None	I
E/L	0.3052	likely_benign	0.3692	ambiguous	0.022	Stabilizing	0.754	D	0.678	prob.neutral	None	None	None	None	I
E/M	0.3883	ambiguous	0.458	ambiguous	0.197	Stabilizing	0.994	D	0.717	prob.delet.	None	None	None	None	I
E/N	0.4045	ambiguous	0.4774	ambiguous	-0.064	Destabilizing	0.978	D	0.605	neutral	None	None	None	None	I
E/P	0.6819	likely_pathogenic	0.7145	pathogenic	-0.124	Destabilizing	0.019	N	0.417	neutral	None	None	None	None	I
E/Q	0.1999	likely_benign	0.2295	benign	-0.042	Destabilizing	0.97	D	0.629	neutral	N	0.472938947	None	None	I
E/R	0.4689	ambiguous	0.576	pathogenic	0.399	Stabilizing	0.978	D	0.603	neutral	None	None	None	None	I
E/S	0.3444	ambiguous	0.3936	ambiguous	-0.236	Destabilizing	0.86	D	0.62	neutral	None	None	None	None	I
E/T	0.3242	likely_benign	0.3844	ambiguous	-0.075	Destabilizing	0.86	D	0.689	prob.neutral	None	None	None	None	I
E/V	0.1294	likely_benign	0.1689	benign	-0.124	Destabilizing	0.014	N	0.428	neutral	N	0.493873933	None	None	I
E/W	0.9545	likely_pathogenic	0.9692	pathogenic	-0.249	Destabilizing	0.998	D	0.784	deleterious	None	None	None	None	I
E/Y	0.7076	likely_pathogenic	0.7764	pathogenic	-0.159	Destabilizing	0.978	D	0.723	prob.delet.	None	None	None	None	I

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.