TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13898	41917;41918;41919	chr2:178635632;178635631;178635630	chr2:179500359;179500358;179500357
N2AB	12257	36994;36995;36996	chr2:178635632;178635631;178635630	chr2:179500359;179500358;179500357
N2A	11330	34213;34214;34215	chr2:178635632;178635631;178635630	chr2:179500359;179500358;179500357
N2B	4833	14722;14723;14724	chr2:178635632;178635631;178635630	chr2:179500359;179500358;179500357
Novex-1	4958	15097;15098;15099	chr2:178635632;178635631;178635630	chr2:179500359;179500358;179500357
Novex-2	5025	15298;15299;15300	chr2:178635632;178635631;178635630	chr2:179500359;179500358;179500357
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-89
• Domain position: 23
• Structural Position: 38
• Q(SASA): 0.7685
• 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
A/G	None	None	0.181	N	0.264	0.09	0.326074293725	gnomAD-4.0.0	1.6384E-06	None	None	None	None	N	None	0	0	None	0	2.82056E-05	None	0	0	0	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
A/C	0.6577	likely_pathogenic	0.6861	pathogenic	-0.754	Destabilizing	0.887	D	0.315	neutral	None	None	None	None	N
A/D	0.7555	likely_pathogenic	0.8634	pathogenic	-0.79	Destabilizing	0.507	D	0.486	neutral	None	None	None	None	N
A/E	0.61	likely_pathogenic	0.7502	pathogenic	-0.937	Destabilizing	0.181	N	0.502	neutral	N	0.446763097	None	None	N
A/F	0.4408	ambiguous	0.5263	ambiguous	-0.867	Destabilizing	0.001	N	0.251	neutral	None	None	None	None	N
A/G	0.2796	likely_benign	0.3582	ambiguous	-0.294	Destabilizing	0.181	N	0.264	neutral	N	0.45338285	None	None	N
A/H	0.6979	likely_pathogenic	0.7693	pathogenic	-0.308	Destabilizing	0.507	D	0.423	neutral	None	None	None	None	N
A/I	0.3528	ambiguous	0.4401	ambiguous	-0.33	Destabilizing	0.128	N	0.4	neutral	None	None	None	None	N
A/K	0.7338	likely_pathogenic	0.8405	pathogenic	-0.764	Destabilizing	0.227	N	0.497	neutral	None	None	None	None	N
A/L	0.2797	likely_benign	0.3272	benign	-0.33	Destabilizing	0.057	N	0.367	neutral	None	None	None	None	N
A/M	0.3937	ambiguous	0.4683	ambiguous	-0.505	Destabilizing	0.676	D	0.384	neutral	None	None	None	None	N
A/N	0.5777	likely_pathogenic	0.6671	pathogenic	-0.409	Destabilizing	0.507	D	0.501	neutral	None	None	None	None	N
A/P	0.7666	likely_pathogenic	0.8614	pathogenic	-0.273	Destabilizing	0.612	D	0.471	neutral	N	0.452720731	None	None	N
A/Q	0.5353	ambiguous	0.6274	pathogenic	-0.697	Destabilizing	0.676	D	0.458	neutral	None	None	None	None	N
A/R	0.6309	likely_pathogenic	0.7385	pathogenic	-0.258	Destabilizing	0.507	D	0.473	neutral	None	None	None	None	N
A/S	0.1316	likely_benign	0.151	benign	-0.542	Destabilizing	0.1	N	0.274	neutral	N	0.424867333	None	None	N
A/T	0.163	likely_benign	0.2119	benign	-0.621	Destabilizing	0.001	N	0.184	neutral	N	0.44129151	None	None	N
A/V	0.1748	likely_benign	0.2256	benign	-0.273	Destabilizing	None	N	0.106	neutral	N	0.430765861	None	None	N
A/W	0.8792	likely_pathogenic	0.9168	pathogenic	-1.017	Destabilizing	0.887	D	0.448	neutral	None	None	None	None	N
A/Y	0.6551	likely_pathogenic	0.7229	pathogenic	-0.682	Destabilizing	0.004	N	0.32	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.