TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4896	14911;14912;14913	chr2:178735760;178735759;178735758	chr2:179600487;179600486;179600485
N2AB	4579	13960;13961;13962	chr2:178735760;178735759;178735758	chr2:179600487;179600486;179600485
N2A	3652	11179;11180;11181	chr2:178735760;178735759;178735758	chr2:179600487;179600486;179600485
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: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-32
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.5058
• 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/S	None	None	0.001	N	0.19	0.083	0.0806252709748	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	1.26695E-04	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
P/A	0.0649	likely_benign	0.0577	benign	-0.438	Destabilizing	0.001	N	0.188	neutral	N	0.435694601	None	None	N
P/C	0.4483	ambiguous	0.3346	benign	-0.555	Destabilizing	0.909	D	0.578	neutral	None	None	None	None	N
P/D	0.3022	likely_benign	0.2385	benign	-0.581	Destabilizing	0.272	N	0.415	neutral	None	None	None	None	N
P/E	0.2363	likely_benign	0.1925	benign	-0.707	Destabilizing	0.157	N	0.356	neutral	None	None	None	None	N
P/F	0.4167	ambiguous	0.3262	benign	-0.738	Destabilizing	0.726	D	0.576	neutral	None	None	None	None	N
P/G	0.2483	likely_benign	0.1861	benign	-0.554	Destabilizing	0.157	N	0.421	neutral	None	None	None	None	N
P/H	0.1665	likely_benign	0.1354	benign	-0.204	Destabilizing	0.883	D	0.532	neutral	N	0.453636257	None	None	N
P/I	0.2988	likely_benign	0.2406	benign	-0.282	Destabilizing	0.567	D	0.564	neutral	None	None	None	None	N
P/K	0.268	likely_benign	0.2114	benign	-0.505	Destabilizing	0.157	N	0.405	neutral	None	None	None	None	N
P/L	0.1184	likely_benign	0.1036	benign	-0.282	Destabilizing	0.124	N	0.495	neutral	N	0.461829693	None	None	N
P/M	0.2603	likely_benign	0.2152	benign	-0.348	Destabilizing	0.909	D	0.533	neutral	None	None	None	None	N
P/N	0.2155	likely_benign	0.172	benign	-0.188	Destabilizing	0.396	N	0.48	neutral	None	None	None	None	N
P/Q	0.1501	likely_benign	0.1281	benign	-0.468	Destabilizing	0.033	N	0.299	neutral	None	None	None	None	N
P/R	0.1833	likely_benign	0.1536	benign	0.044	Stabilizing	0.497	N	0.525	neutral	N	0.501054754	None	None	N
P/S	0.0983	likely_benign	0.0814	benign	-0.466	Destabilizing	0.001	N	0.19	neutral	N	0.444456554	None	None	N
P/T	0.0823	likely_benign	0.0738	benign	-0.501	Destabilizing	0.124	N	0.353	neutral	N	0.438870361	None	None	N
P/V	0.1992	likely_benign	0.1683	benign	-0.3	Destabilizing	0.157	N	0.489	neutral	None	None	None	None	N
P/W	0.5835	likely_pathogenic	0.4495	ambiguous	-0.824	Destabilizing	0.968	D	0.665	neutral	None	None	None	None	N
P/Y	0.3537	ambiguous	0.2704	benign	-0.527	Destabilizing	0.726	D	0.579	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.