TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14414	43465;43466;43467	chr2:178632766;178632765;178632764	chr2:179497493;179497492;179497491
N2AB	12773	38542;38543;38544	chr2:178632766;178632765;178632764	chr2:179497493;179497492;179497491
N2A	11846	35761;35762;35763	chr2:178632766;178632765;178632764	chr2:179497493;179497492;179497491
N2B	5349	16270;16271;16272	chr2:178632766;178632765;178632764	chr2:179497493;179497492;179497491
Novex-1	5474	16645;16646;16647	chr2:178632766;178632765;178632764	chr2:179497493;179497492;179497491
Novex-2	5541	16846;16847;16848	chr2:178632766;178632765;178632764	chr2:179497493;179497492;179497491
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-95
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.1522
• 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/I	None	None	0.999	D	0.509	0.413	0.744054721055	gnomAD-4.0.0	6.8455E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15972E-05	0
L/V	rs2059958801	None	0.999	D	0.488	0.474	0.782390726779	gnomAD-4.0.0	3.42275E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69899E-06	0	3.31466E-05

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	0.8981	likely_pathogenic	0.8976	pathogenic	-2.203	Highly Destabilizing	0.999	D	0.712	prob.delet.	None	None	None	None	N
L/C	0.9436	likely_pathogenic	0.9389	pathogenic	-1.599	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
L/D	0.9983	likely_pathogenic	0.9982	pathogenic	-2.008	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/E	0.9899	likely_pathogenic	0.9892	pathogenic	-1.781	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
L/F	0.7463	likely_pathogenic	0.7621	pathogenic	-1.274	Destabilizing	1.0	D	0.724	prob.delet.	D	0.675662117	None	None	N
L/G	0.9885	likely_pathogenic	0.9871	pathogenic	-2.741	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
L/H	0.9811	likely_pathogenic	0.9802	pathogenic	-2.195	Highly Destabilizing	1.0	D	0.883	deleterious	D	0.733101046	None	None	N
L/I	0.2322	likely_benign	0.246	benign	-0.659	Destabilizing	0.999	D	0.509	neutral	D	0.541331889	None	None	N
L/K	0.987	likely_pathogenic	0.9851	pathogenic	-1.369	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
L/M	0.412	ambiguous	0.4059	ambiguous	-0.806	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
L/N	0.9874	likely_pathogenic	0.9874	pathogenic	-1.669	Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	N
L/P	0.9323	likely_pathogenic	0.9249	pathogenic	-1.153	Destabilizing	1.0	D	0.911	deleterious	D	0.547654362	None	None	N
L/Q	0.9635	likely_pathogenic	0.9587	pathogenic	-1.509	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
L/R	0.9742	likely_pathogenic	0.9675	pathogenic	-1.253	Destabilizing	1.0	D	0.894	deleterious	D	0.734031611	None	None	N
L/S	0.9741	likely_pathogenic	0.9746	pathogenic	-2.447	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
L/T	0.9265	likely_pathogenic	0.9287	pathogenic	-2.067	Highly Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
L/V	0.3079	likely_benign	0.3132	benign	-1.153	Destabilizing	0.999	D	0.488	neutral	D	0.660530465	None	None	N
L/W	0.9718	likely_pathogenic	0.9699	pathogenic	-1.573	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
L/Y	0.9843	likely_pathogenic	0.9844	pathogenic	-1.26	Destabilizing	1.0	D	0.864	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.