TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10048	30367;30368;30369	chr2:178704228;178704227;178704226	chr2:179568955;179568954;179568953
N2AB	9731	29416;29417;29418	chr2:178704228;178704227;178704226	chr2:179568955;179568954;179568953
N2A	8804	26635;26636;26637	chr2:178704228;178704227;178704226	chr2:179568955;179568954;179568953
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-85
• Domain position: 60
• Structural Position: 141
• Q(SASA): 0.2428
• 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	0.27	None	0.357	0.113	0.296329037015	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
A/C	0.7178	likely_pathogenic	0.7222	pathogenic	-1.129	Destabilizing	0.995	D	0.443	neutral	None	None	None	None	N
A/D	0.4051	ambiguous	0.3866	ambiguous	-1.857	Destabilizing	0.704	D	0.501	neutral	None	None	None	None	N
A/E	0.3065	likely_benign	0.2895	benign	-1.928	Destabilizing	0.27	N	0.389	neutral	None	None	None	None	N
A/F	0.4637	ambiguous	0.4675	ambiguous	-1.363	Destabilizing	0.893	D	0.58	neutral	None	None	None	None	N
A/G	0.2218	likely_benign	0.2275	benign	-1.195	Destabilizing	0.425	N	0.322	neutral	None	None	None	None	N
A/H	0.5404	ambiguous	0.5548	ambiguous	-1.206	Destabilizing	0.007	N	0.364	neutral	None	None	None	None	N
A/I	0.3588	ambiguous	0.378	ambiguous	-0.633	Destabilizing	0.543	D	0.498	neutral	None	None	None	None	N
A/K	0.4269	ambiguous	0.4475	ambiguous	-1.208	Destabilizing	0.003	N	0.166	neutral	None	None	None	None	N
A/L	0.2424	likely_benign	0.251	benign	-0.633	Destabilizing	0.329	N	0.386	neutral	None	None	None	None	N
A/M	0.3012	likely_benign	0.3103	benign	-0.431	Destabilizing	0.176	N	0.289	neutral	None	None	None	None	N
A/N	0.3408	ambiguous	0.3369	benign	-1.017	Destabilizing	0.704	D	0.501	neutral	None	None	None	None	N
A/P	0.5296	ambiguous	0.5691	pathogenic	-0.719	Destabilizing	0.784	D	0.499	neutral	None	None	None	None	N
A/Q	0.3482	ambiguous	0.3599	ambiguous	-1.315	Destabilizing	0.031	N	0.24	neutral	None	None	None	None	N
A/R	0.3772	ambiguous	0.3794	ambiguous	-0.712	Destabilizing	0.031	N	0.201	neutral	None	None	None	None	N
A/S	0.1077	likely_benign	0.1018	benign	-1.27	Destabilizing	0.029	N	0.153	neutral	None	None	None	None	N
A/T	0.0981	likely_benign	0.0964	benign	-1.269	Destabilizing	0.27	N	0.357	neutral	None	None	None	None	N
A/V	0.1884	likely_benign	0.1929	benign	-0.719	Destabilizing	0.27	N	0.368	neutral	None	None	None	None	N
A/W	0.8298	likely_pathogenic	0.83	pathogenic	-1.61	Destabilizing	0.995	D	0.563	neutral	None	None	None	None	N
A/Y	0.6075	likely_pathogenic	0.6114	pathogenic	-1.238	Destabilizing	0.893	D	0.591	neutral	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.