TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31322	94189;94190;94191	chr2:178547662;178547661;178547660	chr2:179412389;179412388;179412387
N2AB	29681	89266;89267;89268	chr2:178547662;178547661;178547660	chr2:179412389;179412388;179412387
N2A	28754	86485;86486;86487	chr2:178547662;178547661;178547660	chr2:179412389;179412388;179412387
N2B	22257	66994;66995;66996	chr2:178547662;178547661;178547660	chr2:179412389;179412388;179412387
Novex-1	22382	67369;67370;67371	chr2:178547662;178547661;178547660	chr2:179412389;179412388;179412387
Novex-2	22449	67570;67571;67572	chr2:178547662;178547661;178547660	chr2:179412389;179412388;179412387
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-116
• Domain position: 15
• Structural Position: 16
• Q(SASA): 0.1972
• 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/L	rs879213271	None	0.885	N	0.478	0.308	None	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	0.1891	likely_benign	0.197	benign	-0.467	Destabilizing	0.76	D	0.397	neutral	N	0.51188369	None	None	N
S/C	0.2283	likely_benign	0.2238	benign	-0.438	Destabilizing	0.999	D	0.497	neutral	None	None	None	None	N
S/D	0.6902	likely_pathogenic	0.6638	pathogenic	-1.169	Destabilizing	0.953	D	0.444	neutral	None	None	None	None	N
S/E	0.9083	likely_pathogenic	0.895	pathogenic	-1.167	Destabilizing	0.953	D	0.446	neutral	None	None	None	None	N
S/F	0.592	likely_pathogenic	0.574	pathogenic	-0.731	Destabilizing	0.993	D	0.593	neutral	None	None	None	None	N
S/G	0.1607	likely_benign	0.1604	benign	-0.716	Destabilizing	0.953	D	0.397	neutral	None	None	None	None	N
S/H	0.7686	likely_pathogenic	0.7162	pathogenic	-1.324	Destabilizing	0.999	D	0.491	neutral	None	None	None	None	N
S/I	0.6307	likely_pathogenic	0.6277	pathogenic	0.086	Stabilizing	0.986	D	0.592	neutral	None	None	None	None	N
S/K	0.9599	likely_pathogenic	0.948	pathogenic	-0.823	Destabilizing	0.953	D	0.448	neutral	None	None	None	None	N
S/L	0.1909	likely_benign	0.2051	benign	0.086	Stabilizing	0.885	D	0.478	neutral	N	0.500378618	None	None	N
S/M	0.3579	ambiguous	0.3462	ambiguous	0.519	Stabilizing	0.999	D	0.497	neutral	None	None	None	None	N
S/N	0.3134	likely_benign	0.2857	benign	-0.96	Destabilizing	0.953	D	0.473	neutral	None	None	None	None	N
S/P	0.9575	likely_pathogenic	0.9586	pathogenic	-0.065	Destabilizing	0.991	D	0.514	neutral	N	0.488591348	None	None	N
S/Q	0.8792	likely_pathogenic	0.8559	pathogenic	-1.158	Destabilizing	0.993	D	0.495	neutral	None	None	None	None	N
S/R	0.9498	likely_pathogenic	0.9382	pathogenic	-0.66	Destabilizing	0.986	D	0.506	neutral	None	None	None	None	N
S/T	0.0734	likely_benign	0.0748	benign	-0.802	Destabilizing	0.079	N	0.191	neutral	N	0.384991455	None	None	N
S/V	0.5383	ambiguous	0.5384	ambiguous	-0.065	Destabilizing	0.91	D	0.486	neutral	None	None	None	None	N
S/W	0.7932	likely_pathogenic	0.7706	pathogenic	-0.814	Destabilizing	0.999	D	0.624	neutral	None	None	None	None	N
S/Y	0.5501	ambiguous	0.5287	ambiguous	-0.494	Destabilizing	0.998	D	0.595	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.