TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30239	90940;90941;90942	chr2:178552185;178552184;178552183	chr2:179416912;179416911;179416910
N2AB	28598	86017;86018;86019	chr2:178552185;178552184;178552183	chr2:179416912;179416911;179416910
N2A	27671	83236;83237;83238	chr2:178552185;178552184;178552183	chr2:179416912;179416911;179416910
N2B	21174	63745;63746;63747	chr2:178552185;178552184;178552183	chr2:179416912;179416911;179416910
Novex-1	21299	64120;64121;64122	chr2:178552185;178552184;178552183	chr2:179416912;179416911;179416910
Novex-2	21366	64321;64322;64323	chr2:178552185;178552184;178552183	chr2:179416912;179416911;179416910
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-108
• Domain position: 16
• Structural Position: 17
• Q(SASA): 0.2281
• 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
A/T	rs879126335	None	1.0	N	0.747	0.357	None	gnomAD-4.0.0	1.5914E-06	None	None	None	None	N	None	5.65483E-05	0	None	0	0	None	0	0	0	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
A/C	0.6641	likely_pathogenic	0.6507	pathogenic	-1.07	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
A/D	0.8056	likely_pathogenic	0.6993	pathogenic	-2.273	Highly Destabilizing	1.0	D	0.805	deleterious	N	0.484753017	None	None	N
A/E	0.6975	likely_pathogenic	0.5926	pathogenic	-2.318	Highly Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
A/F	0.7628	likely_pathogenic	0.7298	pathogenic	-1.303	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
A/G	0.2493	likely_benign	0.2179	benign	-1.312	Destabilizing	1.0	D	0.505	neutral	N	0.500453188	None	None	N
A/H	0.8581	likely_pathogenic	0.8224	pathogenic	-1.414	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
A/I	0.6589	likely_pathogenic	0.6136	pathogenic	-0.614	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
A/K	0.8941	likely_pathogenic	0.8444	pathogenic	-1.365	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
A/L	0.5897	likely_pathogenic	0.5452	ambiguous	-0.614	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
A/M	0.5298	ambiguous	0.4958	ambiguous	-0.367	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
A/N	0.6242	likely_pathogenic	0.5499	ambiguous	-1.199	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
A/P	0.6047	likely_pathogenic	0.5439	ambiguous	-0.735	Destabilizing	1.0	D	0.784	deleterious	N	0.496527449	None	None	N
A/Q	0.7246	likely_pathogenic	0.6732	pathogenic	-1.456	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
A/R	0.8556	likely_pathogenic	0.7996	pathogenic	-0.903	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
A/S	0.1292	likely_benign	0.1233	benign	-1.406	Destabilizing	1.0	D	0.514	neutral	N	0.459083782	None	None	N
A/T	0.2711	likely_benign	0.2267	benign	-1.385	Destabilizing	1.0	D	0.747	deleterious	N	0.494815411	None	None	N
A/V	0.3698	ambiguous	0.325	benign	-0.735	Destabilizing	1.0	D	0.657	neutral	N	0.483284976	None	None	N
A/W	0.9311	likely_pathogenic	0.9225	pathogenic	-1.646	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
A/Y	0.8044	likely_pathogenic	0.7695	pathogenic	-1.282	Destabilizing	1.0	D	0.802	deleterious	None	None	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.