TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20776	62551;62552;62553	chr2:178589399;178589398;178589397	chr2:179454126;179454125;179454124
N2AB	19135	57628;57629;57630	chr2:178589399;178589398;178589397	chr2:179454126;179454125;179454124
N2A	18208	54847;54848;54849	chr2:178589399;178589398;178589397	chr2:179454126;179454125;179454124
N2B	11711	35356;35357;35358	chr2:178589399;178589398;178589397	chr2:179454126;179454125;179454124
Novex-1	11836	35731;35732;35733	chr2:178589399;178589398;178589397	chr2:179454126;179454125;179454124
Novex-2	11903	35932;35933;35934	chr2:178589399;178589398;178589397	chr2:179454126;179454125;179454124
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-122
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.6088
• 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
S/N	rs752393957	0.071	0.549	N	0.371	0.059	0.0954503805726	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
S/N	rs752393957	0.071	0.549	N	0.371	0.059	0.0954503805726	gnomAD-4.0.0	1.36867E-06	None	None	None	None	I	None	0	2.23754E-05	None	0	0	None	0	0	8.99548E-07	0	0
S/R	None	None	0.81	N	0.395	0.157	0.19670166235	gnomAD-4.0.0	1.59197E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85914E-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
S/A	0.0688	likely_benign	0.0729	benign	-0.279	Destabilizing	0.009	N	0.111	neutral	None	None	None	None	I
S/C	0.139	likely_benign	0.1822	benign	-0.696	Destabilizing	0.97	D	0.348	neutral	N	0.507677444	None	None	I
S/D	0.4002	ambiguous	0.4505	ambiguous	-0.284	Destabilizing	0.617	D	0.347	neutral	None	None	None	None	I
S/E	0.452	ambiguous	0.5126	ambiguous	-0.382	Destabilizing	0.617	D	0.277	neutral	None	None	None	None	I
S/F	0.2686	likely_benign	0.3142	benign	-1.032	Destabilizing	0.85	D	0.411	neutral	None	None	None	None	I
S/G	0.0882	likely_benign	0.0949	benign	-0.269	Destabilizing	0.334	N	0.309	neutral	N	0.469465773	None	None	I
S/H	0.3548	ambiguous	0.3985	ambiguous	-0.438	Destabilizing	0.992	D	0.347	neutral	None	None	None	None	I
S/I	0.188	likely_benign	0.2273	benign	-0.413	Destabilizing	0.173	N	0.326	neutral	N	0.451477445	None	None	I
S/K	0.5876	likely_pathogenic	0.6444	pathogenic	-0.579	Destabilizing	0.617	D	0.277	neutral	None	None	None	None	I
S/L	0.1094	likely_benign	0.1264	benign	-0.413	Destabilizing	0.25	N	0.316	neutral	None	None	None	None	I
S/M	0.1764	likely_benign	0.2202	benign	-0.476	Destabilizing	0.85	D	0.355	neutral	None	None	None	None	I
S/N	0.1377	likely_benign	0.1578	benign	-0.437	Destabilizing	0.549	D	0.371	neutral	N	0.450437295	None	None	I
S/P	0.1192	likely_benign	0.124	benign	-0.351	Destabilizing	0.92	D	0.391	neutral	None	None	None	None	I
S/Q	0.393	ambiguous	0.4407	ambiguous	-0.592	Destabilizing	0.92	D	0.401	neutral	None	None	None	None	I
S/R	0.5656	likely_pathogenic	0.6147	pathogenic	-0.351	Destabilizing	0.81	D	0.395	neutral	N	0.399469757	None	None	I
S/T	0.0763	likely_benign	0.0851	benign	-0.558	Destabilizing	0.016	N	0.112	neutral	N	0.439836299	None	None	I
S/V	0.166	likely_benign	0.2029	benign	-0.351	Destabilizing	0.002	N	0.193	neutral	None	None	None	None	I
S/W	0.3764	ambiguous	0.4273	ambiguous	-1.148	Destabilizing	0.992	D	0.421	neutral	None	None	None	None	I
S/Y	0.2479	likely_benign	0.2855	benign	-0.852	Destabilizing	0.92	D	0.4	neutral	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.