TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27400	82423;82424;82425	chr2:178563934;178563933;178563932	chr2:179428661;179428660;179428659
N2AB	25759	77500;77501;77502	chr2:178563934;178563933;178563932	chr2:179428661;179428660;179428659
N2A	24832	74719;74720;74721	chr2:178563934;178563933;178563932	chr2:179428661;179428660;179428659
N2B	18335	55228;55229;55230	chr2:178563934;178563933;178563932	chr2:179428661;179428660;179428659
Novex-1	18460	55603;55604;55605	chr2:178563934;178563933;178563932	chr2:179428661;179428660;179428659
Novex-2	18527	55804;55805;55806	chr2:178563934;178563933;178563932	chr2:179428661;179428660;179428659
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-87
• Domain position: 32
• Structural Position: 33
• Q(SASA): 0.1409
• 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
A/T	None	None	0.955	N	0.704	0.323	0.31291088546	gnomAD-4.0.0	1.36848E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79902E-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
A/C	0.4317	ambiguous	0.4175	ambiguous	-0.83	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
A/D	0.4139	ambiguous	0.404	ambiguous	-1.038	Destabilizing	0.993	D	0.828	deleterious	N	0.509264673	None	None	N
A/E	0.5113	ambiguous	0.5164	ambiguous	-1.118	Destabilizing	0.995	D	0.803	deleterious	None	None	None	None	N
A/F	0.6027	likely_pathogenic	0.6168	pathogenic	-1.227	Destabilizing	0.999	D	0.832	deleterious	None	None	None	None	N
A/G	0.1788	likely_benign	0.1739	benign	-1.113	Destabilizing	0.955	D	0.633	neutral	N	0.503333204	None	None	N
A/H	0.6869	likely_pathogenic	0.6979	pathogenic	-1.247	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
A/I	0.6224	likely_pathogenic	0.6513	pathogenic	-0.54	Destabilizing	0.998	D	0.819	deleterious	None	None	None	None	N
A/K	0.8198	likely_pathogenic	0.8316	pathogenic	-1.084	Destabilizing	0.995	D	0.809	deleterious	None	None	None	None	N
A/L	0.4558	ambiguous	0.4397	ambiguous	-0.54	Destabilizing	0.983	D	0.768	deleterious	None	None	None	None	N
A/M	0.4204	ambiguous	0.4274	ambiguous	-0.351	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
A/N	0.3747	ambiguous	0.3941	ambiguous	-0.701	Destabilizing	0.995	D	0.821	deleterious	None	None	None	None	N
A/P	0.9738	likely_pathogenic	0.972	pathogenic	-0.625	Destabilizing	0.997	D	0.821	deleterious	N	0.499970425	None	None	N
A/Q	0.5831	likely_pathogenic	0.5897	pathogenic	-0.939	Destabilizing	0.998	D	0.825	deleterious	None	None	None	None	N
A/R	0.7627	likely_pathogenic	0.7743	pathogenic	-0.665	Destabilizing	0.995	D	0.817	deleterious	None	None	None	None	N
A/S	0.0796	likely_benign	0.077	benign	-1.019	Destabilizing	0.568	D	0.529	neutral	N	0.406348162	None	None	N
A/T	0.1502	likely_benign	0.1569	benign	-1.012	Destabilizing	0.955	D	0.704	prob.neutral	N	0.513017054	None	None	N
A/V	0.3083	likely_benign	0.3336	benign	-0.625	Destabilizing	0.977	D	0.747	deleterious	N	0.478699392	None	None	N
A/W	0.9006	likely_pathogenic	0.8977	pathogenic	-1.471	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
A/Y	0.6925	likely_pathogenic	0.6872	pathogenic	-1.106	Destabilizing	1.0	D	0.831	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.