TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24392	73399;73400;73401	chr2:178572958;178572957;178572956	chr2:179437685;179437684;179437683
N2AB	22751	68476;68477;68478	chr2:178572958;178572957;178572956	chr2:179437685;179437684;179437683
N2A	21824	65695;65696;65697	chr2:178572958;178572957;178572956	chr2:179437685;179437684;179437683
N2B	15327	46204;46205;46206	chr2:178572958;178572957;178572956	chr2:179437685;179437684;179437683
Novex-1	15452	46579;46580;46581	chr2:178572958;178572957;178572956	chr2:179437685;179437684;179437683
Novex-2	15519	46780;46781;46782	chr2:178572958;178572957;178572956	chr2:179437685;179437684;179437683
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-65
• Domain position: 70
• Structural Position: 100
• Q(SASA): 0.6464
• 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
N/S	None	None	0.822	D	0.467	0.305	0.199424873507	gnomAD-4.0.0	2.05335E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69888E-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
N/A	0.3198	likely_benign	0.3334	benign	-0.505	Destabilizing	0.754	D	0.575	neutral	None	None	None	None	N
N/C	0.3338	likely_benign	0.357	ambiguous	0.281	Stabilizing	0.998	D	0.737	prob.delet.	None	None	None	None	N
N/D	0.1511	likely_benign	0.148	benign	-0.421	Destabilizing	0.822	D	0.48	neutral	N	0.488195967	None	None	N
N/E	0.3472	ambiguous	0.3461	ambiguous	-0.415	Destabilizing	0.86	D	0.491	neutral	None	None	None	None	N
N/F	0.5718	likely_pathogenic	0.5735	pathogenic	-0.572	Destabilizing	0.978	D	0.685	prob.neutral	None	None	None	None	N
N/G	0.2215	likely_benign	0.2374	benign	-0.755	Destabilizing	0.019	N	0.262	neutral	None	None	None	None	N
N/H	0.104	likely_benign	0.1121	benign	-0.744	Destabilizing	0.032	N	0.317	neutral	N	0.507301803	None	None	N
N/I	0.4244	ambiguous	0.4363	ambiguous	0.089	Stabilizing	0.97	D	0.688	prob.neutral	N	0.520454537	None	None	N
N/K	0.2004	likely_benign	0.206	benign	-0.24	Destabilizing	0.822	D	0.488	neutral	N	0.50532029	None	None	N
N/L	0.3412	ambiguous	0.3438	ambiguous	0.089	Stabilizing	0.956	D	0.657	neutral	None	None	None	None	N
N/M	0.3639	ambiguous	0.369	ambiguous	0.572	Stabilizing	0.998	D	0.661	neutral	None	None	None	None	N
N/P	0.8901	likely_pathogenic	0.8963	pathogenic	-0.08	Destabilizing	0.993	D	0.649	neutral	None	None	None	None	N
N/Q	0.2679	likely_benign	0.28	benign	-0.734	Destabilizing	0.956	D	0.452	neutral	None	None	None	None	N
N/R	0.308	likely_benign	0.3278	benign	-0.165	Destabilizing	0.956	D	0.456	neutral	None	None	None	None	N
N/S	0.1333	likely_benign	0.1393	benign	-0.5	Destabilizing	0.822	D	0.467	neutral	D	0.523212618	None	None	N
N/T	0.2134	likely_benign	0.2177	benign	-0.344	Destabilizing	0.904	D	0.486	neutral	N	0.485460568	None	None	N
N/V	0.4427	ambiguous	0.4549	ambiguous	-0.08	Destabilizing	0.978	D	0.675	neutral	None	None	None	None	N
N/W	0.7652	likely_pathogenic	0.7845	pathogenic	-0.458	Destabilizing	0.998	D	0.738	prob.delet.	None	None	None	None	N
N/Y	0.1719	likely_benign	0.176	benign	-0.25	Destabilizing	0.942	D	0.651	neutral	N	0.480661175	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.