TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25556	76891;76892;76893	chr2:178569466;178569465;178569464	chr2:179434193;179434192;179434191
N2AB	23915	71968;71969;71970	chr2:178569466;178569465;178569464	chr2:179434193;179434192;179434191
N2A	22988	69187;69188;69189	chr2:178569466;178569465;178569464	chr2:179434193;179434192;179434191
N2B	16491	49696;49697;49698	chr2:178569466;178569465;178569464	chr2:179434193;179434192;179434191
Novex-1	16616	50071;50072;50073	chr2:178569466;178569465;178569464	chr2:179434193;179434192;179434191
Novex-2	16683	50272;50273;50274	chr2:178569466;178569465;178569464	chr2:179434193;179434192;179434191
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-135
• Domain position: 43
• Structural Position: 122
• Q(SASA): 0.1748
• 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
I/V	rs1707317089	None	0.019	N	0.303	0.055	0.564872276104	gnomAD-4.0.0	6.846E-06	None	None	None	None	N	None	0	2.23844E-05	None	0	0	None	0	0	8.09886E-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
I/A	0.1491	likely_benign	0.1683	benign	-0.841	Destabilizing	0.025	N	0.382	neutral	None	None	None	None	N
I/C	0.4686	ambiguous	0.5126	ambiguous	-0.735	Destabilizing	0.859	D	0.571	neutral	None	None	None	None	N
I/D	0.3847	ambiguous	0.4195	ambiguous	-0.403	Destabilizing	0.22	N	0.531	neutral	None	None	None	None	N
I/E	0.3005	likely_benign	0.3011	benign	-0.469	Destabilizing	0.055	N	0.444	neutral	None	None	None	None	N
I/F	0.1286	likely_benign	0.1361	benign	-0.678	Destabilizing	0.124	N	0.452	neutral	None	None	None	None	N
I/G	0.3699	ambiguous	0.42	ambiguous	-1.047	Destabilizing	0.104	N	0.514	neutral	None	None	None	None	N
I/H	0.2445	likely_benign	0.254	benign	-0.28	Destabilizing	0.667	D	0.633	neutral	None	None	None	None	N
I/K	0.1912	likely_benign	0.1793	benign	-0.612	Destabilizing	0.042	N	0.448	neutral	N	0.417731096	None	None	N
I/L	0.092	likely_benign	0.0915	benign	-0.4	Destabilizing	None	N	0.107	neutral	N	0.449979588	None	None	N
I/M	0.0754	likely_benign	0.0747	benign	-0.462	Destabilizing	0.003	N	0.249	neutral	N	0.473221807	None	None	N
I/N	0.1076	likely_benign	0.1145	benign	-0.455	Destabilizing	0.22	N	0.571	neutral	None	None	None	None	N
I/P	0.8011	likely_pathogenic	0.8445	pathogenic	-0.514	Destabilizing	0.364	N	0.619	neutral	None	None	None	None	N
I/Q	0.1747	likely_benign	0.1761	benign	-0.651	Destabilizing	0.001	N	0.389	neutral	None	None	None	None	N
I/R	0.1726	likely_benign	0.1649	benign	-0.034	Destabilizing	None	N	0.438	neutral	N	0.386386682	None	None	N
I/S	0.1291	likely_benign	0.1399	benign	-0.921	Destabilizing	0.104	N	0.437	neutral	None	None	None	None	N
I/T	0.1057	likely_benign	0.1148	benign	-0.875	Destabilizing	0.081	N	0.421	neutral	N	0.401878996	None	None	N
I/V	0.0594	likely_benign	0.0622	benign	-0.514	Destabilizing	0.019	N	0.303	neutral	N	0.456617558	None	None	N
I/W	0.6452	likely_pathogenic	0.6839	pathogenic	-0.715	Destabilizing	0.958	D	0.617	neutral	None	None	None	None	N
I/Y	0.3432	ambiguous	0.3673	ambiguous	-0.48	Destabilizing	0.364	N	0.575	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.