TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14462	43609;43610;43611	chr2:178632622;178632621;178632620	chr2:179497349;179497348;179497347
N2AB	12821	38686;38687;38688	chr2:178632622;178632621;178632620	chr2:179497349;179497348;179497347
N2A	11894	35905;35906;35907	chr2:178632622;178632621;178632620	chr2:179497349;179497348;179497347
N2B	5397	16414;16415;16416	chr2:178632622;178632621;178632620	chr2:179497349;179497348;179497347
Novex-1	5522	16789;16790;16791	chr2:178632622;178632621;178632620	chr2:179497349;179497348;179497347
Novex-2	5589	16990;16991;16992	chr2:178632622;178632621;178632620	chr2:179497349;179497348;179497347
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-95
• Domain position: 55
• Structural Position: 136
• Q(SASA): 0.1233
• 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/Y	None	None	0.4	N	0.493	0.247	0.319686207203	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
H/A	0.7812	likely_pathogenic	0.8088	pathogenic	-2.018	Highly Destabilizing	0.993	D	0.735	prob.delet.	None	None	None	None	N
H/C	0.3525	ambiguous	0.3271	benign	-1.35	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
H/D	0.8601	likely_pathogenic	0.8847	pathogenic	-2.271	Highly Destabilizing	0.999	D	0.755	deleterious	D	0.651833333	None	None	N
H/E	0.8461	likely_pathogenic	0.8726	pathogenic	-2.029	Highly Destabilizing	0.998	D	0.665	neutral	None	None	None	None	N
H/F	0.4112	ambiguous	0.3854	ambiguous	-0.237	Destabilizing	0.991	D	0.759	deleterious	None	None	None	None	N
H/G	0.8624	likely_pathogenic	0.8749	pathogenic	-2.45	Highly Destabilizing	0.998	D	0.747	deleterious	None	None	None	None	N
H/I	0.5683	likely_pathogenic	0.589	pathogenic	-0.686	Destabilizing	0.998	D	0.823	deleterious	None	None	None	None	N
H/K	0.8157	likely_pathogenic	0.8446	pathogenic	-0.813	Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	N
H/L	0.3037	likely_benign	0.3081	benign	-0.686	Destabilizing	0.98	D	0.769	deleterious	D	0.568887586	None	None	N
H/M	0.7528	likely_pathogenic	0.7549	pathogenic	-1.027	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
H/N	0.3699	ambiguous	0.4199	ambiguous	-2.03	Highly Destabilizing	0.997	D	0.667	neutral	D	0.557219266	None	None	N
H/P	0.91	likely_pathogenic	0.9214	pathogenic	-1.128	Destabilizing	0.999	D	0.79	deleterious	D	0.613824781	None	None	N
H/Q	0.6096	likely_pathogenic	0.6612	pathogenic	-1.613	Destabilizing	0.999	D	0.721	prob.delet.	N	0.506142582	None	None	N
H/R	0.4754	ambiguous	0.5514	ambiguous	-0.809	Destabilizing	0.999	D	0.709	prob.delet.	N	0.494806517	None	None	N
H/S	0.7193	likely_pathogenic	0.7555	pathogenic	-2.26	Highly Destabilizing	0.993	D	0.743	deleterious	None	None	None	None	N
H/T	0.7613	likely_pathogenic	0.8068	pathogenic	-1.872	Destabilizing	0.998	D	0.763	deleterious	None	None	None	None	N
H/V	0.5527	ambiguous	0.5721	pathogenic	-1.128	Destabilizing	0.996	D	0.794	deleterious	None	None	None	None	N
H/W	0.547	ambiguous	0.5079	ambiguous	0.501	Stabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
H/Y	0.1034	likely_benign	0.0978	benign	0.165	Stabilizing	0.4	N	0.493	neutral	N	0.497800774	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.