TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5277	16054;16055;16056	chr2:178733464;178733463;178733462	chr2:179598191;179598190;179598189
N2AB	4960	15103;15104;15105	chr2:178733464;178733463;178733462	chr2:179598191;179598190;179598189
N2A	4033	12322;12323;12324	chr2:178733464;178733463;178733462	chr2:179598191;179598190;179598189
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: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-36
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.2734
• 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
P/T	None	None	0.956	N	0.407	0.251	0.276898752692	gnomAD-4.0.0	1.20036E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31255E-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
P/A	0.111	likely_benign	0.1159	benign	-0.631	Destabilizing	0.9	D	0.412	neutral	N	0.453646469	None	None	N
P/C	0.7499	likely_pathogenic	0.7606	pathogenic	-0.64	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
P/D	0.8124	likely_pathogenic	0.7474	pathogenic	-0.215	Destabilizing	0.983	D	0.402	neutral	None	None	None	None	N
P/E	0.6588	likely_pathogenic	0.5867	pathogenic	-0.317	Destabilizing	0.983	D	0.417	neutral	None	None	None	None	N
P/F	0.6736	likely_pathogenic	0.6412	pathogenic	-0.773	Destabilizing	0.999	D	0.662	neutral	None	None	None	None	N
P/G	0.5446	ambiguous	0.533	ambiguous	-0.802	Destabilizing	0.983	D	0.453	neutral	None	None	None	None	N
P/H	0.4359	ambiguous	0.3846	ambiguous	-0.329	Destabilizing	1.0	D	0.576	neutral	N	0.478903333	None	None	N
P/I	0.4097	ambiguous	0.4564	ambiguous	-0.325	Destabilizing	0.998	D	0.652	neutral	None	None	None	None	N
P/K	0.728	likely_pathogenic	0.6525	pathogenic	-0.42	Destabilizing	0.983	D	0.411	neutral	None	None	None	None	N
P/L	0.2047	likely_benign	0.2158	benign	-0.325	Destabilizing	0.997	D	0.593	neutral	N	0.488990887	None	None	N
P/M	0.4024	ambiguous	0.4288	ambiguous	-0.265	Destabilizing	1.0	D	0.574	neutral	None	None	None	None	N
P/N	0.5548	ambiguous	0.5405	ambiguous	-0.132	Destabilizing	0.995	D	0.499	neutral	None	None	None	None	N
P/Q	0.3765	ambiguous	0.3596	ambiguous	-0.394	Destabilizing	0.998	D	0.467	neutral	None	None	None	None	N
P/R	0.5259	ambiguous	0.4448	ambiguous	0.104	Stabilizing	0.997	D	0.573	neutral	N	0.434395091	None	None	N
P/S	0.2113	likely_benign	0.1939	benign	-0.587	Destabilizing	0.418	N	0.306	neutral	N	0.440658981	None	None	N
P/T	0.1484	likely_benign	0.1424	benign	-0.582	Destabilizing	0.956	D	0.407	neutral	N	0.440125327	None	None	N
P/V	0.2831	likely_benign	0.3162	benign	-0.391	Destabilizing	0.998	D	0.497	neutral	None	None	None	None	N
P/W	0.8768	likely_pathogenic	0.8457	pathogenic	-0.83	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
P/Y	0.727	likely_pathogenic	0.6572	pathogenic	-0.523	Destabilizing	0.999	D	0.663	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.