TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35507	106744;106745;106746	chr2:178529972;178529971;178529970	chr2:179394699;179394698;179394697
N2AB	33866	101821;101822;101823	chr2:178529972;178529971;178529970	chr2:179394699;179394698;179394697
N2A	32939	99040;99041;99042	chr2:178529972;178529971;178529970	chr2:179394699;179394698;179394697
N2B	26442	79549;79550;79551	chr2:178529972;178529971;178529970	chr2:179394699;179394698;179394697
Novex-1	26567	79924;79925;79926	chr2:178529972;178529971;178529970	chr2:179394699;179394698;179394697
Novex-2	26634	80125;80126;80127	chr2:178529972;178529971;178529970	chr2:179394699;179394698;179394697
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-166
• Domain position: 88
• Structural Position: 174
• Q(SASA): 0.0895
• 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/F	None	None	0.996	N	0.789	0.503	0.565865824572	gnomAD-4.0.0	1.64877E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.89902E-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	0.8401	likely_pathogenic	0.8551	pathogenic	-2.919	Highly Destabilizing	0.979	D	0.702	prob.neutral	None	None	None	None	N
L/C	0.8987	likely_pathogenic	0.9125	pathogenic	-2.478	Highly Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
L/D	0.9958	likely_pathogenic	0.9957	pathogenic	-3.305	Highly Destabilizing	0.999	D	0.877	deleterious	None	None	None	None	N
L/E	0.9764	likely_pathogenic	0.9756	pathogenic	-3.08	Highly Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
L/F	0.4231	ambiguous	0.4587	ambiguous	-1.856	Destabilizing	0.996	D	0.789	deleterious	N	0.511084285	None	None	N
L/G	0.9558	likely_pathogenic	0.9622	pathogenic	-3.482	Highly Destabilizing	0.999	D	0.876	deleterious	None	None	None	None	N
L/H	0.9476	likely_pathogenic	0.9497	pathogenic	-2.878	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
L/I	0.1332	likely_benign	0.1349	benign	-1.277	Destabilizing	0.877	D	0.636	neutral	N	0.474872093	None	None	N
L/K	0.9614	likely_pathogenic	0.9608	pathogenic	-2.308	Highly Destabilizing	0.999	D	0.868	deleterious	None	None	None	None	N
L/M	0.2279	likely_benign	0.2348	benign	-1.293	Destabilizing	0.997	D	0.751	deleterious	None	None	None	None	N
L/N	0.9744	likely_pathogenic	0.9746	pathogenic	-2.688	Highly Destabilizing	0.999	D	0.887	deleterious	None	None	None	None	N
L/P	0.9878	likely_pathogenic	0.9889	pathogenic	-1.807	Destabilizing	0.999	D	0.879	deleterious	None	None	None	None	N
L/Q	0.9153	likely_pathogenic	0.9153	pathogenic	-2.56	Highly Destabilizing	0.999	D	0.877	deleterious	None	None	None	None	N
L/R	0.9369	likely_pathogenic	0.9349	pathogenic	-1.956	Destabilizing	0.999	D	0.868	deleterious	None	None	None	None	N
L/S	0.9639	likely_pathogenic	0.9666	pathogenic	-3.425	Highly Destabilizing	0.996	D	0.861	deleterious	D	0.541812293	None	None	N
L/T	0.8857	likely_pathogenic	0.8911	pathogenic	-3.046	Highly Destabilizing	0.979	D	0.789	deleterious	None	None	None	None	N
L/V	0.1701	likely_benign	0.1677	benign	-1.807	Destabilizing	0.316	N	0.333	neutral	N	0.48844947	None	None	N
L/W	0.8483	likely_pathogenic	0.8713	pathogenic	-2.226	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
L/Y	0.8581	likely_pathogenic	0.8748	pathogenic	-2.005	Highly Destabilizing	0.999	D	0.823	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.