TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6257	18994;18995;18996	chr2:178729387;178729386;178729385	chr2:179594114;179594113;179594112
N2AB	5940	18043;18044;18045	chr2:178729387;178729386;178729385	chr2:179594114;179594113;179594112
N2A	5013	15262;15263;15264	chr2:178729387;178729386;178729385	chr2:179594114;179594113;179594112
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-46
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.2504
• 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/R	rs371299041	-1.134	0.007	N	0.404	0.112	None	gnomAD-2.1.1	1.07E-05	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	1.57E-05	0
H/R	rs371299041	-1.134	0.007	N	0.404	0.112	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
H/R	rs371299041	-1.134	0.007	N	0.404	0.112	None	gnomAD-4.0.0	1.17755E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	1.64582E-04	1.27155E-05	3.29337E-05	0
H/Y	None	None	0.175	N	0.478	0.108	0.286465849087	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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
H/A	0.1814	likely_benign	0.1743	benign	-0.954	Destabilizing	0.004	N	0.372	neutral	None	None	None	None	N
H/C	0.117	likely_benign	0.1165	benign	-0.379	Destabilizing	0.788	D	0.517	neutral	None	None	None	None	N
H/D	0.1966	likely_benign	0.1989	benign	-0.59	Destabilizing	None	N	0.257	neutral	N	0.506006229	None	None	N
H/E	0.2049	likely_benign	0.2054	benign	-0.514	Destabilizing	None	N	0.202	neutral	None	None	None	None	N
H/F	0.2052	likely_benign	0.2084	benign	-0.144	Destabilizing	0.245	N	0.52	neutral	None	None	None	None	N
H/G	0.2457	likely_benign	0.2274	benign	-1.283	Destabilizing	0.004	N	0.369	neutral	None	None	None	None	N
H/I	0.1651	likely_benign	0.1733	benign	-0.057	Destabilizing	0.085	N	0.555	neutral	None	None	None	None	N
H/K	0.1477	likely_benign	0.1542	benign	-0.893	Destabilizing	None	N	0.251	neutral	None	None	None	None	N
H/L	0.0939	likely_benign	0.0919	benign	-0.057	Destabilizing	0.014	N	0.444	neutral	N	0.458001638	None	None	N
H/M	0.3104	likely_benign	0.3077	benign	-0.163	Destabilizing	0.245	N	0.489	neutral	None	None	None	None	N
H/N	0.0898	likely_benign	0.0965	benign	-0.823	Destabilizing	None	N	0.207	neutral	N	0.474491243	None	None	N
H/P	0.6529	likely_pathogenic	0.5896	pathogenic	-0.335	Destabilizing	0.065	N	0.518	neutral	N	0.50174635	None	None	N
H/Q	0.1104	likely_benign	0.107	benign	-0.644	Destabilizing	None	N	0.241	neutral	N	0.433375339	None	None	N
H/R	0.0714	likely_benign	0.0674	benign	-1.131	Destabilizing	0.007	N	0.404	neutral	N	0.453305108	None	None	N
H/S	0.1582	likely_benign	0.1497	benign	-0.969	Destabilizing	None	N	0.251	neutral	None	None	None	None	N
H/T	0.1575	likely_benign	0.1601	benign	-0.796	Destabilizing	0.009	N	0.399	neutral	None	None	None	None	N
H/V	0.1555	likely_benign	0.1591	benign	-0.335	Destabilizing	0.044	N	0.502	neutral	None	None	None	None	N
H/W	0.2881	likely_benign	0.2542	benign	0.071	Stabilizing	0.788	D	0.524	neutral	None	None	None	None	N
H/Y	0.0791	likely_benign	0.0826	benign	0.312	Stabilizing	0.175	N	0.478	neutral	N	0.508873176	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.