TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27456	82591;82592;82593	chr2:178563766;178563765;178563764	chr2:179428493;179428492;179428491
N2AB	25815	77668;77669;77670	chr2:178563766;178563765;178563764	chr2:179428493;179428492;179428491
N2A	24888	74887;74888;74889	chr2:178563766;178563765;178563764	chr2:179428493;179428492;179428491
N2B	18391	55396;55397;55398	chr2:178563766;178563765;178563764	chr2:179428493;179428492;179428491
Novex-1	18516	55771;55772;55773	chr2:178563766;178563765;178563764	chr2:179428493;179428492;179428491
Novex-2	18583	55972;55973;55974	chr2:178563766;178563765;178563764	chr2:179428493;179428492;179428491
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-87
• Domain position: 88
• Structural Position: 121
• Q(SASA): 0.1292
• 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	rs1233877374	None	0.994	N	0.679	0.255	0.489311470972	gnomAD-4.0.0	1.36846E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79897E-06	0	0
L/M	None	None	0.983	N	0.701	0.268	0.365509141856	gnomAD-4.0.0	1.36846E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79897E-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	0.3658	ambiguous	0.3929	ambiguous	-2.397	Highly Destabilizing	0.128	N	0.476	neutral	None	None	None	None	N
L/C	0.5456	ambiguous	0.5579	ambiguous	-1.675	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
L/D	0.9737	likely_pathogenic	0.9746	pathogenic	-2.614	Highly Destabilizing	0.975	D	0.763	deleterious	None	None	None	None	N
L/E	0.7493	likely_pathogenic	0.7696	pathogenic	-2.443	Highly Destabilizing	0.95	D	0.72	prob.delet.	None	None	None	None	N
L/F	0.5207	ambiguous	0.5711	pathogenic	-1.413	Destabilizing	0.994	D	0.679	prob.neutral	N	0.516421477	None	None	N
L/G	0.8198	likely_pathogenic	0.818	pathogenic	-2.878	Highly Destabilizing	0.975	D	0.716	prob.delet.	None	None	None	None	N
L/H	0.7194	likely_pathogenic	0.7425	pathogenic	-2.283	Highly Destabilizing	0.997	D	0.795	deleterious	None	None	None	None	N
L/I	0.1279	likely_benign	0.1461	benign	-1.034	Destabilizing	0.957	D	0.644	neutral	None	None	None	None	N
L/K	0.6607	likely_pathogenic	0.671	pathogenic	-1.792	Destabilizing	0.95	D	0.667	neutral	None	None	None	None	N
L/M	0.181	likely_benign	0.2007	benign	-1.037	Destabilizing	0.983	D	0.701	prob.neutral	N	0.516674966	None	None	N
L/N	0.8598	likely_pathogenic	0.864	pathogenic	-1.974	Destabilizing	0.975	D	0.799	deleterious	None	None	None	None	N
L/P	0.9824	likely_pathogenic	0.9821	pathogenic	-1.467	Destabilizing	0.987	D	0.799	deleterious	None	None	None	None	N
L/Q	0.4031	ambiguous	0.418	ambiguous	-1.933	Destabilizing	0.253	N	0.527	neutral	None	None	None	None	N
L/R	0.4873	ambiguous	0.5021	ambiguous	-1.421	Destabilizing	0.95	D	0.706	prob.neutral	None	None	None	None	N
L/S	0.5955	likely_pathogenic	0.6244	pathogenic	-2.628	Highly Destabilizing	0.805	D	0.643	neutral	N	0.471925675	None	None	N
L/T	0.3544	ambiguous	0.3772	ambiguous	-2.331	Highly Destabilizing	0.916	D	0.664	neutral	None	None	None	None	N
L/V	0.1164	likely_benign	0.13	benign	-1.467	Destabilizing	0.892	D	0.613	neutral	N	0.517206578	None	None	N
L/W	0.7836	likely_pathogenic	0.8189	pathogenic	-1.751	Destabilizing	0.999	D	0.731	prob.delet.	N	0.516928456	None	None	N
L/Y	0.8273	likely_pathogenic	0.8445	pathogenic	-1.475	Destabilizing	0.996	D	0.735	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.