TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8557	25894;25895;25896	chr2:178715745;178715744;178715743	chr2:179580472;179580471;179580470
N2AB	8240	24943;24944;24945	chr2:178715745;178715744;178715743	chr2:179580472;179580471;179580470
N2A	7313	22162;22163;22164	chr2:178715745;178715744;178715743	chr2:179580472;179580471;179580470
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: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-71
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.4861
• 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
P/T	None	None	0.001	N	0.283	0.047	0.126345400529	gnomAD-4.0.0	1.65379E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.96969E-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	0.0667	likely_benign	0.0625	benign	-0.15	Destabilizing	None	N	0.131	neutral	N	0.432408894	None	None	N
P/C	0.5738	likely_pathogenic	0.4861	ambiguous	-0.547	Destabilizing	0.201	N	0.375	neutral	None	None	None	None	N
P/D	0.4241	ambiguous	0.3297	benign	-0.034	Destabilizing	0.001	N	0.3	neutral	None	None	None	None	N
P/E	0.3384	likely_benign	0.2419	benign	-0.163	Destabilizing	None	N	0.299	neutral	None	None	None	None	N
P/F	0.4673	ambiguous	0.3766	ambiguous	-0.592	Destabilizing	0.214	N	0.391	neutral	None	None	None	None	N
P/G	0.2286	likely_benign	0.195	benign	-0.219	Destabilizing	0.002	N	0.307	neutral	None	None	None	None	N
P/H	0.2156	likely_benign	0.1535	benign	0.057	Stabilizing	0.037	N	0.375	neutral	N	0.509426883	None	None	N
P/I	0.3098	likely_benign	0.229	benign	-0.127	Destabilizing	0.214	N	0.398	neutral	None	None	None	None	N
P/K	0.3382	likely_benign	0.2359	benign	-0.063	Destabilizing	0.008	N	0.295	neutral	None	None	None	None	N
P/L	0.1382	likely_benign	0.1094	benign	-0.127	Destabilizing	0.028	N	0.357	neutral	N	0.494534789	None	None	N
P/M	0.2945	likely_benign	0.2301	benign	-0.215	Destabilizing	0.093	N	0.375	neutral	None	None	None	None	N
P/N	0.2468	likely_benign	0.1773	benign	0.153	Stabilizing	0.002	N	0.337	neutral	None	None	None	None	N
P/Q	0.1659	likely_benign	0.1075	benign	-0.084	Destabilizing	None	N	0.176	neutral	None	None	None	None	N
P/R	0.2555	likely_benign	0.1898	benign	0.348	Stabilizing	0.014	N	0.389	neutral	N	0.499652607	None	None	N
P/S	0.1077	likely_benign	0.086	benign	-0.173	Destabilizing	None	N	0.132	neutral	N	0.41497514	None	None	N
P/T	0.0976	likely_benign	0.0752	benign	-0.205	Destabilizing	0.001	N	0.283	neutral	N	0.489358255	None	None	N
P/V	0.2014	likely_benign	0.1596	benign	-0.104	Destabilizing	0.007	N	0.331	neutral	None	None	None	None	N
P/W	0.6666	likely_pathogenic	0.5604	ambiguous	-0.672	Destabilizing	0.758	D	0.404	neutral	None	None	None	None	N
P/Y	0.4164	ambiguous	0.3277	benign	-0.337	Destabilizing	0.214	N	0.4	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.