TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29861	89806;89807;89808	chr2:178553319;178553318;178553317	chr2:179418046;179418045;179418044
N2AB	28220	84883;84884;84885	chr2:178553319;178553318;178553317	chr2:179418046;179418045;179418044
N2A	27293	82102;82103;82104	chr2:178553319;178553318;178553317	chr2:179418046;179418045;179418044
N2B	20796	62611;62612;62613	chr2:178553319;178553318;178553317	chr2:179418046;179418045;179418044
Novex-1	20921	62986;62987;62988	chr2:178553319;178553318;178553317	chr2:179418046;179418045;179418044
Novex-2	20988	63187;63188;63189	chr2:178553319;178553318;178553317	chr2:179418046;179418045;179418044
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-147
• Domain position: 20
• Structural Position: 33
• Q(SASA): 0.093
• 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
I/F	rs1384879576	-1.434	0.497	N	0.696	0.191	0.461144880706	gnomAD-2.1.1	4.12E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
I/F	rs1384879576	-1.434	0.497	N	0.696	0.191	0.461144880706	gnomAD-4.0.0	1.37576E-06	None	None	None	None	N	None	0	2.23644E-05	None	0	0	None	0	1.73491E-04	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
I/A	0.9178	likely_pathogenic	0.9017	pathogenic	-1.998	Destabilizing	0.157	N	0.755	deleterious	None	None	None	None	N
I/C	0.9202	likely_pathogenic	0.9132	pathogenic	-1.301	Destabilizing	0.909	D	0.773	deleterious	None	None	None	None	N
I/D	0.9974	likely_pathogenic	0.9963	pathogenic	-1.594	Destabilizing	0.726	D	0.859	deleterious	None	None	None	None	N
I/E	0.9915	likely_pathogenic	0.9894	pathogenic	-1.421	Destabilizing	0.726	D	0.858	deleterious	None	None	None	None	N
I/F	0.4674	ambiguous	0.421	ambiguous	-1.123	Destabilizing	0.497	N	0.696	prob.neutral	N	0.470758176	None	None	N
I/G	0.9877	likely_pathogenic	0.9847	pathogenic	-2.464	Highly Destabilizing	0.726	D	0.851	deleterious	None	None	None	None	N
I/H	0.9761	likely_pathogenic	0.9665	pathogenic	-1.543	Destabilizing	0.968	D	0.868	deleterious	None	None	None	None	N
I/K	0.9782	likely_pathogenic	0.9714	pathogenic	-1.431	Destabilizing	0.726	D	0.857	deleterious	None	None	None	None	N
I/L	0.238	likely_benign	0.222	benign	-0.697	Destabilizing	None	N	0.352	neutral	N	0.455754566	None	None	N
I/M	0.3043	likely_benign	0.2926	benign	-0.657	Destabilizing	0.497	N	0.665	neutral	N	0.462617874	None	None	N
I/N	0.9558	likely_pathogenic	0.9416	pathogenic	-1.66	Destabilizing	0.859	D	0.848	deleterious	N	0.48936941	None	None	N
I/P	0.9891	likely_pathogenic	0.9839	pathogenic	-1.107	Destabilizing	0.89	D	0.853	deleterious	None	None	None	None	N
I/Q	0.9718	likely_pathogenic	0.9651	pathogenic	-1.575	Destabilizing	0.89	D	0.869	deleterious	None	None	None	None	N
I/R	0.9678	likely_pathogenic	0.9572	pathogenic	-1.097	Destabilizing	0.726	D	0.845	deleterious	None	None	None	None	N
I/S	0.9288	likely_pathogenic	0.914	pathogenic	-2.382	Highly Destabilizing	0.497	N	0.815	deleterious	N	0.470758176	None	None	N
I/T	0.9351	likely_pathogenic	0.9158	pathogenic	-2.058	Highly Destabilizing	0.124	N	0.783	deleterious	N	0.458894891	None	None	N
I/V	0.1656	likely_benign	0.1579	benign	-1.107	Destabilizing	0.001	N	0.322	neutral	N	0.399024253	None	None	N
I/W	0.9782	likely_pathogenic	0.9683	pathogenic	-1.314	Destabilizing	0.968	D	0.864	deleterious	None	None	None	None	N
I/Y	0.9038	likely_pathogenic	0.8773	pathogenic	-1.036	Destabilizing	0.726	D	0.771	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.