TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26575	79948;79949;79950	chr2:178566409;178566408;178566407	chr2:179431136;179431135;179431134
N2AB	24934	75025;75026;75027	chr2:178566409;178566408;178566407	chr2:179431136;179431135;179431134
N2A	24007	72244;72245;72246	chr2:178566409;178566408;178566407	chr2:179431136;179431135;179431134
N2B	17510	52753;52754;52755	chr2:178566409;178566408;178566407	chr2:179431136;179431135;179431134
Novex-1	17635	53128;53129;53130	chr2:178566409;178566408;178566407	chr2:179431136;179431135;179431134
Novex-2	17702	53329;53330;53331	chr2:178566409;178566408;178566407	chr2:179431136;179431135;179431134
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-81
• Domain position: 89
• Structural Position: 121
• Q(SASA): 0.1899
• Predicted PPI site: I

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
T/P	rs1705878064	None	0.317	N	0.608	0.064	0.110078149338	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/P	rs1705878064	None	0.317	N	0.608	0.064	0.110078149338	gnomAD-4.0.0	2.03E-06	None	None	None	None	I	None	3.49357E-05	0	None	0	0	None	0	0	0	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
T/A	0.0463	likely_benign	0.0487	benign	-0.914	Destabilizing	None	N	0.278	neutral	N	0.353369321	None	None	I
T/C	0.2819	likely_benign	0.2739	benign	-0.817	Destabilizing	0.824	D	0.609	neutral	None	None	None	None	I
T/D	0.3899	ambiguous	0.3682	ambiguous	-1.307	Destabilizing	0.38	N	0.599	neutral	None	None	None	None	I
T/E	0.3715	ambiguous	0.3506	ambiguous	-1.259	Destabilizing	0.149	N	0.561	neutral	None	None	None	None	I
T/F	0.2781	likely_benign	0.2613	benign	-0.891	Destabilizing	0.555	D	0.622	neutral	None	None	None	None	I
T/G	0.1457	likely_benign	0.1616	benign	-1.207	Destabilizing	0.081	N	0.564	neutral	None	None	None	None	I
T/H	0.3527	ambiguous	0.3309	benign	-1.523	Destabilizing	0.935	D	0.637	neutral	None	None	None	None	I
T/I	0.1408	likely_benign	0.1329	benign	-0.204	Destabilizing	0.062	N	0.533	neutral	N	0.442065741	None	None	I
T/K	0.3531	ambiguous	0.3314	benign	-0.955	Destabilizing	0.117	N	0.566	neutral	N	0.501844763	None	None	I
T/L	0.1151	likely_benign	0.1103	benign	-0.204	Destabilizing	0.035	N	0.532	neutral	None	None	None	None	I
T/M	0.0935	likely_benign	0.0915	benign	0.085	Stabilizing	0.555	D	0.62	neutral	None	None	None	None	I
T/N	0.1256	likely_benign	0.1229	benign	-1.155	Destabilizing	0.555	D	0.621	neutral	None	None	None	None	I
T/P	0.3151	likely_benign	0.3292	benign	-0.409	Destabilizing	0.317	N	0.608	neutral	N	0.501844763	None	None	I
T/Q	0.308	likely_benign	0.2951	benign	-1.319	Destabilizing	0.555	D	0.605	neutral	None	None	None	None	I
T/R	0.3167	likely_benign	0.2906	benign	-0.75	Destabilizing	0.317	N	0.606	neutral	N	0.501671405	None	None	I
T/S	0.0843	likely_benign	0.0835	benign	-1.313	Destabilizing	0.027	N	0.553	neutral	N	0.361532152	None	None	I
T/V	0.0929	likely_benign	0.0896	benign	-0.409	Destabilizing	0.001	N	0.283	neutral	None	None	None	None	I
T/W	0.7464	likely_pathogenic	0.7253	pathogenic	-0.893	Destabilizing	0.935	D	0.655	neutral	None	None	None	None	I
T/Y	0.3498	ambiguous	0.3379	benign	-0.609	Destabilizing	0.555	D	0.64	neutral	None	None	None	None	I

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.