TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4815	14668;14669;14670	chr2:178736003;178736002;178736001	chr2:179600730;179600729;179600728
N2AB	4498	13717;13718;13719	chr2:178736003;178736002;178736001	chr2:179600730;179600729;179600728
N2A	3571	10936;10937;10938	chr2:178736003;178736002;178736001	chr2:179600730;179600729;179600728
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: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-31
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.4984
• 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
I/F	rs1284454958	-1.058	0.029	N	0.337	0.139	0.404870348458	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.89E-06	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
I/A	0.1656	likely_benign	0.1812	benign	-2.112	Highly Destabilizing	0.014	N	0.353	neutral	None	None	None	None	I
I/C	0.3727	ambiguous	0.4745	ambiguous	-1.307	Destabilizing	0.628	D	0.465	neutral	None	None	None	None	I
I/D	0.4092	ambiguous	0.4921	ambiguous	-1.586	Destabilizing	0.072	N	0.505	neutral	None	None	None	None	I
I/E	0.2874	likely_benign	0.3422	ambiguous	-1.521	Destabilizing	0.016	N	0.415	neutral	None	None	None	None	I
I/F	0.1	likely_benign	0.119	benign	-1.384	Destabilizing	0.029	N	0.337	neutral	N	0.510099179	None	None	I
I/G	0.374	ambiguous	0.4387	ambiguous	-2.515	Highly Destabilizing	0.072	N	0.464	neutral	None	None	None	None	I
I/H	0.2016	likely_benign	0.2356	benign	-1.697	Destabilizing	None	N	0.399	neutral	None	None	None	None	I
I/K	0.234	likely_benign	0.2815	benign	-1.523	Destabilizing	0.016	N	0.424	neutral	None	None	None	None	I
I/L	0.0512	likely_benign	0.0579	benign	-1.035	Destabilizing	None	N	0.17	neutral	N	0.503852014	None	None	I
I/M	0.0813	likely_benign	0.0907	benign	-0.8	Destabilizing	0.093	N	0.452	neutral	N	0.504371629	None	None	I
I/N	0.1474	likely_benign	0.1633	benign	-1.409	Destabilizing	0.055	N	0.5	neutral	N	0.465536795	None	None	I
I/P	0.5518	ambiguous	0.6274	pathogenic	-1.366	Destabilizing	0.136	N	0.561	neutral	None	None	None	None	I
I/Q	0.1776	likely_benign	0.1999	benign	-1.518	Destabilizing	None	N	0.451	neutral	None	None	None	None	I
I/R	0.1495	likely_benign	0.1874	benign	-0.95	Destabilizing	0.038	N	0.505	neutral	None	None	None	None	I
I/S	0.1346	likely_benign	0.1425	benign	-2.107	Highly Destabilizing	0.024	N	0.415	neutral	N	0.392261002	None	None	I
I/T	0.1187	likely_benign	0.1249	benign	-1.917	Destabilizing	0.024	N	0.362	neutral	N	0.419625238	None	None	I
I/V	0.0789	likely_benign	0.0805	benign	-1.366	Destabilizing	0.005	N	0.271	neutral	N	0.497822157	None	None	I
I/W	0.419	ambiguous	0.5658	pathogenic	-1.515	Destabilizing	0.864	D	0.495	neutral	None	None	None	None	I
I/Y	0.253	likely_benign	0.3168	benign	-1.302	Destabilizing	0.072	N	0.451	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.