TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26833	80722;80723;80724	chr2:178565635;178565634;178565633	chr2:179430362;179430361;179430360
N2AB	25192	75799;75800;75801	chr2:178565635;178565634;178565633	chr2:179430362;179430361;179430360
N2A	24265	73018;73019;73020	chr2:178565635;178565634;178565633	chr2:179430362;179430361;179430360
N2B	17768	53527;53528;53529	chr2:178565635;178565634;178565633	chr2:179430362;179430361;179430360
Novex-1	17893	53902;53903;53904	chr2:178565635;178565634;178565633	chr2:179430362;179430361;179430360
Novex-2	17960	54103;54104;54105	chr2:178565635;178565634;178565633	chr2:179430362;179430361;179430360
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Fn3-83
• Domain position: 54
• Structural Position: 77
• Q(SASA): 0.3605
• 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
S/T	None	None	0.01	N	0.127	0.134	0.0986583533028	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
S/A	0.0928	likely_benign	0.0898	benign	-0.539	Destabilizing	0.01	N	0.135	neutral	N	0.428766448	None	None	N
S/C	0.0895	likely_benign	0.0884	benign	-0.312	Destabilizing	0.013	N	0.257	neutral	N	0.427459727	None	None	N
S/D	0.7161	likely_pathogenic	0.7338	pathogenic	-0.77	Destabilizing	0.704	D	0.389	neutral	None	None	None	None	N
S/E	0.7575	likely_pathogenic	0.789	pathogenic	-0.628	Destabilizing	0.704	D	0.349	neutral	None	None	None	None	N
S/F	0.4866	ambiguous	0.4924	ambiguous	-0.35	Destabilizing	0.759	D	0.511	neutral	N	0.475058885	None	None	N
S/G	0.1281	likely_benign	0.1126	benign	-0.914	Destabilizing	0.495	N	0.345	neutral	None	None	None	None	N
S/H	0.6015	likely_pathogenic	0.6614	pathogenic	-1.33	Destabilizing	0.893	D	0.439	neutral	None	None	None	None	N
S/I	0.2327	likely_benign	0.2383	benign	0.393	Stabilizing	0.704	D	0.483	neutral	None	None	None	None	N
S/K	0.8647	likely_pathogenic	0.8956	pathogenic	-0.347	Destabilizing	0.704	D	0.347	neutral	None	None	None	None	N
S/L	0.1702	likely_benign	0.1619	benign	0.393	Stabilizing	0.329	N	0.43	neutral	None	None	None	None	N
S/M	0.256	likely_benign	0.2502	benign	0.296	Stabilizing	0.981	D	0.439	neutral	None	None	None	None	N
S/N	0.2213	likely_benign	0.2334	benign	-0.779	Destabilizing	0.704	D	0.439	neutral	None	None	None	None	N
S/P	0.7001	likely_pathogenic	0.7177	pathogenic	0.119	Stabilizing	0.927	D	0.47	neutral	N	0.438036506	None	None	N
S/Q	0.7036	likely_pathogenic	0.742	pathogenic	-0.6	Destabilizing	0.944	D	0.455	neutral	None	None	None	None	N
S/R	0.8241	likely_pathogenic	0.8602	pathogenic	-0.634	Destabilizing	0.944	D	0.473	neutral	None	None	None	None	N
S/T	0.0769	likely_benign	0.0737	benign	-0.529	Destabilizing	0.01	N	0.127	neutral	N	0.41710666	None	None	N
S/V	0.1575	likely_benign	0.1661	benign	0.119	Stabilizing	0.543	D	0.447	neutral	None	None	None	None	N
S/W	0.6612	likely_pathogenic	0.6766	pathogenic	-0.585	Destabilizing	0.985	D	0.537	neutral	None	None	None	None	N
S/Y	0.4006	ambiguous	0.4356	ambiguous	-0.158	Destabilizing	0.006	N	0.365	neutral	N	0.494260722	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.