TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2753	8482;8483;8484	chr2:178770535;178770534;178770533	chr2:179635262;179635261;179635260
N2AB	2753	8482;8483;8484	chr2:178770535;178770534;178770533	chr2:179635262;179635261;179635260
N2A	2753	8482;8483;8484	chr2:178770535;178770534;178770533	chr2:179635262;179635261;179635260
N2B	2707	8344;8345;8346	chr2:178770535;178770534;178770533	chr2:179635262;179635261;179635260
Novex-1	2707	8344;8345;8346	chr2:178770535;178770534;178770533	chr2:179635262;179635261;179635260
Novex-2	2707	8344;8345;8346	chr2:178770535;178770534;178770533	chr2:179635262;179635261;179635260
Novex-3	2753	8482;8483;8484	chr2:178770535;178770534;178770533	chr2:179635262;179635261;179635260

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-17
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.1424
• 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
Y/C	rs2091310789	None	1.0	D	0.798	0.585	0.701639087021	gnomAD-4.0.0	1.5905E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85652E-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
Y/A	0.8245	likely_pathogenic	0.8852	pathogenic	-3.149	Highly Destabilizing	0.998	D	0.652	neutral	None	None	None	None	N
Y/C	0.3481	ambiguous	0.4261	ambiguous	-2.207	Highly Destabilizing	1.0	D	0.798	deleterious	D	0.570513175	None	None	N
Y/D	0.7918	likely_pathogenic	0.87	pathogenic	-3.26	Highly Destabilizing	1.0	D	0.833	deleterious	D	0.652244966	None	None	N
Y/E	0.8956	likely_pathogenic	0.9397	pathogenic	-3.074	Highly Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
Y/F	0.1275	likely_benign	0.1358	benign	-1.223	Destabilizing	0.434	N	0.315	neutral	N	0.51082682	None	None	N
Y/G	0.8257	likely_pathogenic	0.8847	pathogenic	-3.578	Highly Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
Y/H	0.3652	ambiguous	0.4471	ambiguous	-2.153	Highly Destabilizing	1.0	D	0.725	prob.delet.	D	0.584521428	None	None	N
Y/I	0.6526	likely_pathogenic	0.7308	pathogenic	-1.746	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
Y/K	0.9203	likely_pathogenic	0.9508	pathogenic	-2.384	Highly Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
Y/L	0.6983	likely_pathogenic	0.7723	pathogenic	-1.746	Destabilizing	0.994	D	0.489	neutral	None	None	None	None	N
Y/M	0.7781	likely_pathogenic	0.8343	pathogenic	-1.565	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
Y/N	0.4322	ambiguous	0.5369	ambiguous	-3.116	Highly Destabilizing	1.0	D	0.813	deleterious	D	0.587997354	None	None	N
Y/P	0.9867	likely_pathogenic	0.9924	pathogenic	-2.226	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
Y/Q	0.8361	likely_pathogenic	0.8979	pathogenic	-2.88	Highly Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
Y/R	0.8381	likely_pathogenic	0.888	pathogenic	-2.053	Highly Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
Y/S	0.6517	likely_pathogenic	0.7487	pathogenic	-3.536	Highly Destabilizing	1.0	D	0.769	deleterious	D	0.650001637	None	None	N
Y/T	0.7046	likely_pathogenic	0.7866	pathogenic	-3.225	Highly Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
Y/V	0.5516	ambiguous	0.6331	pathogenic	-2.226	Highly Destabilizing	0.997	D	0.635	neutral	None	None	None	None	N
Y/W	0.5926	likely_pathogenic	0.6271	pathogenic	-0.631	Destabilizing	1.0	D	0.708	prob.delet.	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.