TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15386	46381;46382;46383	chr2:178620365;178620364;178620363	chr2:179485092;179485091;179485090
N2AB	13745	41458;41459;41460	chr2:178620365;178620364;178620363	chr2:179485092;179485091;179485090
N2A	12818	38677;38678;38679	chr2:178620365;178620364;178620363	chr2:179485092;179485091;179485090
N2B	6321	19186;19187;19188	chr2:178620365;178620364;178620363	chr2:179485092;179485091;179485090
Novex-1	6446	19561;19562;19563	chr2:178620365;178620364;178620363	chr2:179485092;179485091;179485090
Novex-2	6513	19762;19763;19764	chr2:178620365;178620364;178620363	chr2:179485092;179485091;179485090
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-105
• Domain position: 85
• Structural Position: 178
• Q(SASA): 0.1662
• 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/T	None	None	0.999	N	0.602	0.454	0.619546946635	gnomAD-4.0.0	1.5998E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.03841E-05
I/V	rs879033914	None	0.985	N	0.288	0.217	0.365317461125	gnomAD-4.0.0	2.05735E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.70267E-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
I/A	0.9594	likely_pathogenic	0.9646	pathogenic	-2.285	Highly Destabilizing	0.998	D	0.443	neutral	None	None	None	None	N
I/C	0.9715	likely_pathogenic	0.9728	pathogenic	-1.397	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
I/D	0.9958	likely_pathogenic	0.9966	pathogenic	-2.019	Highly Destabilizing	0.999	D	0.734	prob.delet.	None	None	None	None	N
I/E	0.9907	likely_pathogenic	0.992	pathogenic	-1.855	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
I/F	0.802	likely_pathogenic	0.8217	pathogenic	-1.305	Destabilizing	0.999	D	0.676	prob.neutral	D	0.53962181	None	None	N
I/G	0.9901	likely_pathogenic	0.9911	pathogenic	-2.77	Highly Destabilizing	0.999	D	0.726	prob.delet.	None	None	None	None	N
I/H	0.989	likely_pathogenic	0.9902	pathogenic	-2.034	Highly Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
I/K	0.9735	likely_pathogenic	0.9751	pathogenic	-1.574	Destabilizing	0.999	D	0.734	prob.delet.	None	None	None	None	N
I/L	0.3977	ambiguous	0.408	ambiguous	-0.923	Destabilizing	0.985	D	0.288	neutral	N	0.449685704	None	None	N
I/M	0.4986	ambiguous	0.516	ambiguous	-0.81	Destabilizing	0.999	D	0.684	prob.neutral	D	0.540385868	None	None	N
I/N	0.9359	likely_pathogenic	0.9475	pathogenic	-1.686	Destabilizing	0.999	D	0.748	deleterious	D	0.541517431	None	None	N
I/P	0.9859	likely_pathogenic	0.9879	pathogenic	-1.354	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
I/Q	0.9817	likely_pathogenic	0.9836	pathogenic	-1.652	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
I/R	0.9612	likely_pathogenic	0.9622	pathogenic	-1.194	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
I/S	0.9567	likely_pathogenic	0.9632	pathogenic	-2.427	Highly Destabilizing	0.999	D	0.673	neutral	D	0.541517431	None	None	N
I/T	0.9357	likely_pathogenic	0.9399	pathogenic	-2.132	Highly Destabilizing	0.999	D	0.602	neutral	N	0.496792983	None	None	N
I/V	0.2076	likely_benign	0.186	benign	-1.354	Destabilizing	0.985	D	0.288	neutral	N	0.379952639	None	None	N
I/W	0.9938	likely_pathogenic	0.9944	pathogenic	-1.575	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
I/Y	0.9701	likely_pathogenic	0.9748	pathogenic	-1.308	Destabilizing	0.999	D	0.677	prob.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.