TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6801	20626;20627;20628	chr2:178725921;178725920;178725919	chr2:179590648;179590647;179590646
N2AB	6484	19675;19676;19677	chr2:178725921;178725920;178725919	chr2:179590648;179590647;179590646
N2A	5557	16894;16895;16896	chr2:178725921;178725920;178725919	chr2:179590648;179590647;179590646
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: 41
• Structural Position: 58
• Q(SASA): 0.1444
• 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/H	None	None	1.0	D	0.795	0.793	0.919573595275	gnomAD-4.0.0	3.18587E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.722E-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	0.8616	likely_pathogenic	0.857	pathogenic	-2.24	Highly Destabilizing	0.996	D	0.546	neutral	None	None	None	None	N
L/C	0.8837	likely_pathogenic	0.8948	pathogenic	-1.361	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
L/D	0.9966	likely_pathogenic	0.9964	pathogenic	-2.801	Highly Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
L/E	0.967	likely_pathogenic	0.9624	pathogenic	-2.528	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
L/F	0.4819	ambiguous	0.4382	ambiguous	-1.453	Destabilizing	0.997	D	0.623	neutral	N	0.5216853	None	None	N
L/G	0.9743	likely_pathogenic	0.9734	pathogenic	-2.763	Highly Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
L/H	0.924	likely_pathogenic	0.9096	pathogenic	-2.275	Highly Destabilizing	1.0	D	0.795	deleterious	D	0.554793165	None	None	N
L/I	0.0768	likely_benign	0.0742	benign	-0.698	Destabilizing	0.008	N	0.238	neutral	N	0.445904706	None	None	N
L/K	0.9473	likely_pathogenic	0.9408	pathogenic	-1.762	Destabilizing	0.983	D	0.749	deleterious	None	None	None	None	N
L/M	0.2329	likely_benign	0.2126	benign	-0.627	Destabilizing	0.992	D	0.674	neutral	None	None	None	None	N
L/N	0.9706	likely_pathogenic	0.9669	pathogenic	-2.338	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
L/P	0.9677	likely_pathogenic	0.9654	pathogenic	-1.199	Destabilizing	1.0	D	0.822	deleterious	D	0.53643542	None	None	N
L/Q	0.8657	likely_pathogenic	0.8395	pathogenic	-2.086	Highly Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
L/R	0.9197	likely_pathogenic	0.9074	pathogenic	-1.732	Destabilizing	0.999	D	0.759	deleterious	D	0.53643542	None	None	N
L/S	0.9606	likely_pathogenic	0.956	pathogenic	-2.907	Highly Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
L/T	0.8774	likely_pathogenic	0.8705	pathogenic	-2.48	Highly Destabilizing	0.997	D	0.678	prob.neutral	None	None	None	None	N
L/V	0.1248	likely_benign	0.1174	benign	-1.199	Destabilizing	0.628	D	0.392	neutral	N	0.480422712	None	None	N
L/W	0.8103	likely_pathogenic	0.7973	pathogenic	-1.809	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
L/Y	0.8607	likely_pathogenic	0.8454	pathogenic	-1.482	Destabilizing	0.996	D	0.726	prob.delet.	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.