TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2943	9052;9053;9054	chr2:178769754;178769753;178769752	chr2:179634481;179634480;179634479
N2AB	2943	9052;9053;9054	chr2:178769754;178769753;178769752	chr2:179634481;179634480;179634479
N2A	2943	9052;9053;9054	chr2:178769754;178769753;178769752	chr2:179634481;179634480;179634479
N2B	2897	8914;8915;8916	chr2:178769754;178769753;178769752	chr2:179634481;179634480;179634479
Novex-1	2897	8914;8915;8916	chr2:178769754;178769753;178769752	chr2:179634481;179634480;179634479
Novex-2	2897	8914;8915;8916	chr2:178769754;178769753;178769752	chr2:179634481;179634480;179634479
Novex-3	2943	9052;9053;9054	chr2:178769754;178769753;178769752	chr2:179634481;179634480;179634479

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-19
• Domain position: 62
• Structural Position: 144
• Q(SASA): 0.0906
• 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
T/I	rs1316613829	None	1.0	N	0.792	0.537	0.55355060856	gnomAD-4.0.0	1.5905E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-05	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
T/A	0.1335	likely_benign	0.1522	benign	-0.234	Destabilizing	0.999	D	0.506	neutral	N	0.478579388	None	None	N
T/C	0.5218	ambiguous	0.5762	pathogenic	-1.11	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
T/D	0.9867	likely_pathogenic	0.9914	pathogenic	-2.758	Highly Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
T/E	0.9813	likely_pathogenic	0.9881	pathogenic	-2.636	Highly Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
T/F	0.9711	likely_pathogenic	0.9784	pathogenic	-0.523	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
T/G	0.8003	likely_pathogenic	0.835	pathogenic	-0.48	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
T/H	0.9655	likely_pathogenic	0.9785	pathogenic	-0.824	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
T/I	0.474	ambiguous	0.5912	pathogenic	0.345	Stabilizing	1.0	D	0.792	deleterious	N	0.492245975	None	None	N
T/K	0.97	likely_pathogenic	0.9827	pathogenic	-0.476	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
T/L	0.3696	ambiguous	0.415	ambiguous	0.345	Stabilizing	0.999	D	0.672	neutral	None	None	None	None	N
T/M	0.3568	ambiguous	0.452	ambiguous	0.166	Stabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
T/N	0.7869	likely_pathogenic	0.8473	pathogenic	-1.4	Destabilizing	1.0	D	0.755	deleterious	D	0.631594757	None	None	N
T/P	0.4602	ambiguous	0.5169	ambiguous	0.181	Stabilizing	1.0	D	0.802	deleterious	N	0.499916241	None	None	N
T/Q	0.9546	likely_pathogenic	0.9694	pathogenic	-1.424	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
T/R	0.9452	likely_pathogenic	0.9649	pathogenic	-0.429	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
T/S	0.4029	ambiguous	0.4789	ambiguous	-1.147	Destabilizing	0.999	D	0.54	neutral	N	0.502014931	None	None	N
T/V	0.2512	likely_benign	0.3056	benign	0.181	Stabilizing	0.999	D	0.59	neutral	None	None	None	None	N
T/W	0.9972	likely_pathogenic	0.9983	pathogenic	-0.93	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
T/Y	0.9816	likely_pathogenic	0.9888	pathogenic	-0.352	Destabilizing	1.0	D	0.785	deleterious	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.