TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7258	21997;21998;21999	chr2:178723235;178723234;178723233	chr2:179587962;179587961;179587960
N2AB	6941	21046;21047;21048	chr2:178723235;178723234;178723233	chr2:179587962;179587961;179587960
N2A	6014	18265;18266;18267	chr2:178723235;178723234;178723233	chr2:179587962;179587961;179587960
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: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-57
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.6329
• 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
P/S	rs761911665	-0.35	0.852	N	0.323	0.279	0.411932830014	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.95E-06	0
P/S	rs761911665	-0.35	0.852	N	0.323	0.279	0.411932830014	gnomAD-4.0.0	1.5918E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85896E-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
P/A	0.1626	likely_benign	0.172	benign	-0.461	Destabilizing	0.826	D	0.32	neutral	N	0.486008725	None	None	I
P/C	0.7124	likely_pathogenic	0.729	pathogenic	-0.662	Destabilizing	0.999	D	0.497	neutral	None	None	None	None	I
P/D	0.4892	ambiguous	0.5017	ambiguous	-0.303	Destabilizing	0.884	D	0.349	neutral	None	None	None	None	I
P/E	0.393	ambiguous	0.4143	ambiguous	-0.414	Destabilizing	0.17	N	0.211	neutral	None	None	None	None	I
P/F	0.686	likely_pathogenic	0.7118	pathogenic	-0.687	Destabilizing	0.997	D	0.469	neutral	None	None	None	None	I
P/G	0.4408	ambiguous	0.4416	ambiguous	-0.585	Destabilizing	0.969	D	0.413	neutral	None	None	None	None	I
P/H	0.3363	likely_benign	0.3475	ambiguous	-0.162	Destabilizing	0.997	D	0.447	neutral	None	None	None	None	I
P/I	0.5984	likely_pathogenic	0.6371	pathogenic	-0.283	Destabilizing	0.982	D	0.476	neutral	None	None	None	None	I
P/K	0.4507	ambiguous	0.4714	ambiguous	-0.471	Destabilizing	0.079	N	0.177	neutral	None	None	None	None	I
P/L	0.2301	likely_benign	0.2588	benign	-0.283	Destabilizing	0.92	D	0.45	neutral	N	0.489820613	None	None	I
P/M	0.5708	likely_pathogenic	0.5967	pathogenic	-0.424	Destabilizing	0.999	D	0.446	neutral	None	None	None	None	I
P/N	0.4278	ambiguous	0.4438	ambiguous	-0.209	Destabilizing	0.969	D	0.448	neutral	None	None	None	None	I
P/Q	0.2799	likely_benign	0.2955	benign	-0.439	Destabilizing	0.92	D	0.36	neutral	N	0.485310708	None	None	I
P/R	0.3076	likely_benign	0.3196	benign	0.028	Stabilizing	0.852	D	0.451	neutral	N	0.511644122	None	None	I
P/S	0.2158	likely_benign	0.2265	benign	-0.554	Destabilizing	0.852	D	0.323	neutral	N	0.487085135	None	None	I
P/T	0.2227	likely_benign	0.2384	benign	-0.565	Destabilizing	0.134	N	0.229	neutral	D	0.526322786	None	None	I
P/V	0.4377	ambiguous	0.4598	ambiguous	-0.309	Destabilizing	0.939	D	0.433	neutral	None	None	None	None	I
P/W	0.7996	likely_pathogenic	0.8098	pathogenic	-0.765	Destabilizing	0.999	D	0.557	neutral	None	None	None	None	I
P/Y	0.6404	likely_pathogenic	0.6601	pathogenic	-0.473	Destabilizing	0.997	D	0.473	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.