TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31296	94111;94112;94113	chr2:178547740;178547739;178547738	chr2:179412467;179412466;179412465
N2AB	29655	89188;89189;89190	chr2:178547740;178547739;178547738	chr2:179412467;179412466;179412465
N2A	28728	86407;86408;86409	chr2:178547740;178547739;178547738	chr2:179412467;179412466;179412465
N2B	22231	66916;66917;66918	chr2:178547740;178547739;178547738	chr2:179412467;179412466;179412465
Novex-1	22356	67291;67292;67293	chr2:178547740;178547739;178547738	chr2:179412467;179412466;179412465
Novex-2	22423	67492;67493;67494	chr2:178547740;178547739;178547738	chr2:179412467;179412466;179412465
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-151
• Domain position: 79
• Structural Position: 165
• Q(SASA): 0.349
• 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
V/I	rs794729534	-0.218	0.014	N	0.229	0.084	0.435808882951	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	1.29182E-04	2.9E-05	None	0	0	None	0	None	0	0	0
V/I	rs794729534	-0.218	0.014	N	0.229	0.084	0.435808882951	gnomAD-3.1.2	2.63E-05	None	None	None	None	I	None	9.65E-05	0	0	0	0	None	0	0	0	0	0
V/I	rs794729534	-0.218	0.014	N	0.229	0.084	0.435808882951	gnomAD-4.0.0	1.15327E-05	None	None	None	None	I	None	1.35272E-04	1.69509E-05	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
V/A	0.1149	likely_benign	0.126	benign	-0.386	Destabilizing	0.489	N	0.417	neutral	N	0.471565581	None	None	I
V/C	0.5358	ambiguous	0.5564	ambiguous	-0.577	Destabilizing	0.998	D	0.546	neutral	None	None	None	None	I
V/D	0.2452	likely_benign	0.262	benign	-0.268	Destabilizing	0.942	D	0.67	neutral	N	0.456193484	None	None	I
V/E	0.1575	likely_benign	0.1683	benign	-0.398	Destabilizing	0.956	D	0.579	neutral	None	None	None	None	I
V/F	0.1401	likely_benign	0.1516	benign	-0.731	Destabilizing	0.942	D	0.506	neutral	N	0.473125806	None	None	I
V/G	0.1289	likely_benign	0.1409	benign	-0.491	Destabilizing	0.822	D	0.609	neutral	N	0.486343033	None	None	I
V/H	0.3812	ambiguous	0.4182	ambiguous	-0.152	Destabilizing	0.998	D	0.67	neutral	None	None	None	None	I
V/I	0.0721	likely_benign	0.0758	benign	-0.268	Destabilizing	0.014	N	0.229	neutral	N	0.460292582	None	None	I
V/K	0.1774	likely_benign	0.1885	benign	-0.332	Destabilizing	0.956	D	0.584	neutral	None	None	None	None	I
V/L	0.1564	likely_benign	0.1739	benign	-0.268	Destabilizing	0.247	N	0.432	neutral	N	0.486516391	None	None	I
V/M	0.0962	likely_benign	0.1044	benign	-0.282	Destabilizing	0.956	D	0.481	neutral	None	None	None	None	I
V/N	0.1572	likely_benign	0.1688	benign	-0.06	Destabilizing	0.956	D	0.673	neutral	None	None	None	None	I
V/P	0.6912	likely_pathogenic	0.7241	pathogenic	-0.273	Destabilizing	0.978	D	0.643	neutral	None	None	None	None	I
V/Q	0.1654	likely_benign	0.181	benign	-0.329	Destabilizing	0.978	D	0.644	neutral	None	None	None	None	I
V/R	0.189	likely_benign	0.1921	benign	0.17	Stabilizing	0.978	D	0.675	neutral	None	None	None	None	I
V/S	0.1049	likely_benign	0.1128	benign	-0.392	Destabilizing	0.193	N	0.399	neutral	None	None	None	None	I
V/T	0.0982	likely_benign	0.1083	benign	-0.425	Destabilizing	0.754	D	0.425	neutral	None	None	None	None	I
V/W	0.6923	likely_pathogenic	0.7178	pathogenic	-0.805	Destabilizing	0.998	D	0.691	prob.neutral	None	None	None	None	I
V/Y	0.4168	ambiguous	0.433	ambiguous	-0.491	Destabilizing	0.978	D	0.509	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.