TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6821	20686;20687;20688	chr2:178725861;178725860;178725859	chr2:179590588;179590587;179590586
N2AB	6504	19735;19736;19737	chr2:178725861;178725860;178725859	chr2:179590588;179590587;179590586
N2A	5577	16954;16955;16956	chr2:178725861;178725860;178725859	chr2:179590588;179590587;179590586
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: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-52
• Domain position: 61
• Structural Position: 141
• Q(SASA): 0.1981
• 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
L/R	None	None	1.0	N	0.785	0.32	0.807681222942	gnomAD-4.0.0	1.5925E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86043E-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
L/A	0.4069	ambiguous	0.3337	benign	-2.147	Highly Destabilizing	0.999	D	0.496	neutral	None	None	None	None	N
L/C	0.6251	likely_pathogenic	0.5863	pathogenic	-1.376	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
L/D	0.866	likely_pathogenic	0.8142	pathogenic	-2.008	Highly Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
L/E	0.6051	likely_pathogenic	0.5428	ambiguous	-1.966	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
L/F	0.1522	likely_benign	0.1288	benign	-1.473	Destabilizing	1.0	D	0.728	prob.delet.	N	0.476704829	None	None	N
L/G	0.6825	likely_pathogenic	0.595	pathogenic	-2.526	Highly Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
L/H	0.3194	likely_benign	0.2697	benign	-1.737	Destabilizing	1.0	D	0.757	deleterious	N	0.505987586	None	None	N
L/I	0.107	likely_benign	0.0981	benign	-1.139	Destabilizing	0.23	N	0.325	neutral	N	0.478320982	None	None	N
L/K	0.4684	ambiguous	0.4236	ambiguous	-1.567	Destabilizing	0.998	D	0.768	deleterious	None	None	None	None	N
L/M	0.1413	likely_benign	0.1235	benign	-0.875	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
L/N	0.5217	ambiguous	0.4098	ambiguous	-1.442	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
L/P	0.7034	likely_pathogenic	0.6652	pathogenic	-1.448	Destabilizing	1.0	D	0.785	deleterious	N	0.506622304	None	None	N
L/Q	0.2267	likely_benign	0.1909	benign	-1.613	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
L/R	0.3307	likely_benign	0.3106	benign	-0.937	Destabilizing	1.0	D	0.785	deleterious	N	0.468679992	None	None	N
L/S	0.3899	ambiguous	0.3149	benign	-2.072	Highly Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
L/T	0.3188	likely_benign	0.2633	benign	-1.916	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
L/V	0.1336	likely_benign	0.1183	benign	-1.448	Destabilizing	0.282	N	0.324	neutral	D	0.526632217	None	None	N
L/W	0.2901	likely_benign	0.2795	benign	-1.607	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
L/Y	0.4244	ambiguous	0.3782	ambiguous	-1.409	Destabilizing	0.999	D	0.795	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.