TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2822	8689;8690;8691	chr2:178770237;178770236;178770235	chr2:179634964;179634963;179634962
N2AB	2822	8689;8690;8691	chr2:178770237;178770236;178770235	chr2:179634964;179634963;179634962
N2A	2822	8689;8690;8691	chr2:178770237;178770236;178770235	chr2:179634964;179634963;179634962
N2B	2776	8551;8552;8553	chr2:178770237;178770236;178770235	chr2:179634964;179634963;179634962
Novex-1	2776	8551;8552;8553	chr2:178770237;178770236;178770235	chr2:179634964;179634963;179634962
Novex-2	2776	8551;8552;8553	chr2:178770237;178770236;178770235	chr2:179634964;179634963;179634962
Novex-3	2822	8689;8690;8691	chr2:178770237;178770236;178770235	chr2:179634964;179634963;179634962

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-18
• Domain position: 28
• Structural Position: 43
• Q(SASA): 0.6193
• 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
T/I	None	None	0.996	N	0.395	0.452	0.583209036909	gnomAD-4.0.0	1.36814E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99294E-07	0	1.65574E-05

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
T/A	0.0978	likely_benign	0.0902	benign	-0.173	Destabilizing	0.826	D	0.339	neutral	N	0.49424768	None	None	I
T/C	0.648	likely_pathogenic	0.6283	pathogenic	-0.226	Destabilizing	0.999	D	0.395	neutral	None	None	None	None	I
T/D	0.363	ambiguous	0.3583	ambiguous	-0.072	Destabilizing	0.02	N	0.18	neutral	None	None	None	None	I
T/E	0.427	ambiguous	0.3842	ambiguous	-0.157	Destabilizing	0.759	D	0.351	neutral	None	None	None	None	I
T/F	0.431	ambiguous	0.4183	ambiguous	-0.729	Destabilizing	0.997	D	0.423	neutral	None	None	None	None	I
T/G	0.2573	likely_benign	0.2728	benign	-0.27	Destabilizing	0.02	N	0.199	neutral	None	None	None	None	I
T/H	0.3226	likely_benign	0.306	benign	-0.439	Destabilizing	0.991	D	0.417	neutral	None	None	None	None	I
T/I	0.3769	ambiguous	0.3336	benign	-0.037	Destabilizing	0.996	D	0.395	neutral	N	0.510904279	None	None	I
T/K	0.3287	likely_benign	0.2875	benign	-0.327	Destabilizing	0.939	D	0.365	neutral	None	None	None	None	I
T/L	0.1751	likely_benign	0.172	benign	-0.037	Destabilizing	0.969	D	0.38	neutral	None	None	None	None	I
T/M	0.1276	likely_benign	0.1157	benign	-0.055	Destabilizing	0.999	D	0.369	neutral	None	None	None	None	I
T/N	0.121	likely_benign	0.1242	benign	-0.036	Destabilizing	0.134	N	0.206	neutral	N	0.432452167	None	None	I
T/P	0.3829	ambiguous	0.3436	ambiguous	-0.056	Destabilizing	0.996	D	0.377	neutral	N	0.40827485	None	None	I
T/Q	0.3435	ambiguous	0.3107	benign	-0.27	Destabilizing	0.991	D	0.392	neutral	None	None	None	None	I
T/R	0.2873	likely_benign	0.2349	benign	0.009	Stabilizing	0.991	D	0.382	neutral	None	None	None	None	I
T/S	0.1149	likely_benign	0.1141	benign	-0.189	Destabilizing	0.826	D	0.363	neutral	N	0.48486702	None	None	I
T/V	0.2596	likely_benign	0.2365	benign	-0.056	Destabilizing	0.99	D	0.291	neutral	None	None	None	None	I
T/W	0.806	likely_pathogenic	0.7784	pathogenic	-0.802	Destabilizing	0.999	D	0.477	neutral	None	None	None	None	I
T/Y	0.4898	ambiguous	0.4602	ambiguous	-0.498	Destabilizing	0.997	D	0.424	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.