TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8014	24265;24266;24267	chr2:178719350;178719349;178719348	chr2:179584077;179584076;179584075
N2AB	7697	23314;23315;23316	chr2:178719350;178719349;178719348	chr2:179584077;179584076;179584075
N2A	6770	20533;20534;20535	chr2:178719350;178719349;178719348	chr2:179584077;179584076;179584075
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-65
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.1474
• 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
I/T	rs1415104830	None	0.896	D	0.687	0.374	0.733027900626	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
I/T	rs1415104830	None	0.896	D	0.687	0.374	0.733027900626	gnomAD-4.0.0	2.47888E-06	None	None	None	None	I	None	4.0062E-05	0	None	0	0	None	0	0	8.47636E-07	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	0.7994	likely_pathogenic	0.8145	pathogenic	-2.019	Highly Destabilizing	0.919	D	0.59	neutral	None	None	None	None	I
I/C	0.9464	likely_pathogenic	0.9463	pathogenic	-1.386	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	I
I/D	0.9876	likely_pathogenic	0.9901	pathogenic	-1.282	Destabilizing	0.996	D	0.755	deleterious	None	None	None	None	I
I/E	0.9759	likely_pathogenic	0.9805	pathogenic	-1.206	Destabilizing	0.988	D	0.746	deleterious	None	None	None	None	I
I/F	0.3772	ambiguous	0.384	ambiguous	-1.344	Destabilizing	0.026	N	0.421	neutral	D	0.534712983	None	None	I
I/G	0.9687	likely_pathogenic	0.9727	pathogenic	-2.425	Highly Destabilizing	0.988	D	0.74	deleterious	None	None	None	None	I
I/H	0.959	likely_pathogenic	0.9629	pathogenic	-1.619	Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	I
I/K	0.9429	likely_pathogenic	0.95	pathogenic	-1.351	Destabilizing	0.976	D	0.741	deleterious	None	None	None	None	I
I/L	0.1727	likely_benign	0.1676	benign	-0.937	Destabilizing	0.211	N	0.435	neutral	N	0.471160149	None	None	I
I/M	0.2128	likely_benign	0.2006	benign	-0.816	Destabilizing	0.437	N	0.461	neutral	D	0.522053117	None	None	I
I/N	0.8847	likely_pathogenic	0.9011	pathogenic	-1.286	Destabilizing	0.995	D	0.759	deleterious	N	0.520041642	None	None	I
I/P	0.8922	likely_pathogenic	0.9277	pathogenic	-1.269	Destabilizing	0.996	D	0.761	deleterious	None	None	None	None	I
I/Q	0.9404	likely_pathogenic	0.9473	pathogenic	-1.364	Destabilizing	0.988	D	0.758	deleterious	None	None	None	None	I
I/R	0.907	likely_pathogenic	0.9175	pathogenic	-0.861	Destabilizing	0.988	D	0.76	deleterious	None	None	None	None	I
I/S	0.8619	likely_pathogenic	0.8757	pathogenic	-2.033	Highly Destabilizing	0.984	D	0.699	prob.neutral	N	0.483326153	None	None	I
I/T	0.8568	likely_pathogenic	0.8803	pathogenic	-1.821	Destabilizing	0.896	D	0.687	prob.neutral	D	0.527979011	None	None	I
I/V	0.1055	likely_benign	0.1043	benign	-1.269	Destabilizing	0.437	N	0.478	neutral	N	0.515703147	None	None	I
I/W	0.9692	likely_pathogenic	0.9696	pathogenic	-1.449	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	I
I/Y	0.8624	likely_pathogenic	0.8612	pathogenic	-1.212	Destabilizing	0.952	D	0.699	prob.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.