TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21518	64777;64778;64779	chr2:178585192;178585191;178585190	chr2:179449919;179449918;179449917
N2AB	19877	59854;59855;59856	chr2:178585192;178585191;178585190	chr2:179449919;179449918;179449917
N2A	18950	57073;57074;57075	chr2:178585192;178585191;178585190	chr2:179449919;179449918;179449917
N2B	12453	37582;37583;37584	chr2:178585192;178585191;178585190	chr2:179449919;179449918;179449917
Novex-1	12578	37957;37958;37959	chr2:178585192;178585191;178585190	chr2:179449919;179449918;179449917
Novex-2	12645	38158;38159;38160	chr2:178585192;178585191;178585190	chr2:179449919;179449918;179449917
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-124
• Domain position: 50
• Structural Position: 130
• Q(SASA): 0.4192
• 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/P	None	None	0.484	N	0.271	0.224	0.36355261348	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
A/C	0.4166	ambiguous	0.4375	ambiguous	-0.727	Destabilizing	0.935	D	0.273	neutral	None	None	None	None	N
A/D	0.2255	likely_benign	0.2529	benign	-0.171	Destabilizing	0.38	N	0.379	neutral	None	None	None	None	N
A/E	0.2446	likely_benign	0.2682	benign	-0.323	Destabilizing	0.117	N	0.275	neutral	N	0.405244589	None	None	N
A/F	0.3376	likely_benign	0.3579	ambiguous	-0.796	Destabilizing	0.555	D	0.391	neutral	None	None	None	None	N
A/G	0.0896	likely_benign	0.1038	benign	-0.128	Destabilizing	None	N	0.166	neutral	N	0.404516657	None	None	N
A/H	0.4244	ambiguous	0.4537	ambiguous	-0.179	Destabilizing	0.935	D	0.404	neutral	None	None	None	None	N
A/I	0.2466	likely_benign	0.2792	benign	-0.269	Destabilizing	0.235	N	0.269	neutral	None	None	None	None	N
A/K	0.4071	ambiguous	0.4661	ambiguous	-0.339	Destabilizing	0.149	N	0.29	neutral	None	None	None	None	N
A/L	0.1639	likely_benign	0.1856	benign	-0.269	Destabilizing	0.081	N	0.232	neutral	None	None	None	None	N
A/M	0.1754	likely_benign	0.1949	benign	-0.336	Destabilizing	0.824	D	0.291	neutral	None	None	None	None	N
A/N	0.1617	likely_benign	0.1867	benign	-0.075	Destabilizing	0.38	N	0.365	neutral	None	None	None	None	N
A/P	0.4881	ambiguous	0.5155	ambiguous	-0.188	Destabilizing	0.484	N	0.271	neutral	N	0.451385097	None	None	N
A/Q	0.3179	likely_benign	0.3569	ambiguous	-0.326	Destabilizing	0.555	D	0.282	neutral	None	None	None	None	N
A/R	0.4164	ambiguous	0.4522	ambiguous	0.037	Stabilizing	0.38	N	0.283	neutral	None	None	None	None	N
A/S	0.0723	likely_benign	0.0752	benign	-0.295	Destabilizing	0.027	N	0.346	neutral	N	0.386352184	None	None	N
A/T	0.07	likely_benign	0.0745	benign	-0.366	Destabilizing	None	N	0.163	neutral	N	0.35466384	None	None	N
A/V	0.1227	likely_benign	0.1341	benign	-0.188	Destabilizing	0.062	N	0.247	neutral	N	0.432105903	None	None	N
A/W	0.6881	likely_pathogenic	0.7154	pathogenic	-0.917	Destabilizing	0.935	D	0.501	neutral	None	None	None	None	N
A/Y	0.4253	ambiguous	0.4499	ambiguous	-0.564	Destabilizing	0.555	D	0.395	neutral	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.