TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7204	21835;21836;21837	chr2:178723490;178723489;178723488	chr2:179588217;179588216;179588215
N2AB	6887	20884;20885;20886	chr2:178723490;178723489;178723488	chr2:179588217;179588216;179588215
N2A	5960	18103;18104;18105	chr2:178723490;178723489;178723488	chr2:179588217;179588216;179588215
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: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-56
• Domain position: 68
• Structural Position: 151
• Q(SASA): 0.2243
• 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/R	rs780624577	-0.175	0.997	N	0.708	0.438	0.448891444097	gnomAD-2.1.1	2.01E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	4.45E-05	0
S/R	rs780624577	-0.175	0.997	N	0.708	0.438	0.448891444097	gnomAD-4.0.0	4.79094E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.29729E-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	0.0896	likely_benign	0.0988	benign	-0.74	Destabilizing	0.246	N	0.208	neutral	None	None	None	None	N
S/C	0.2323	likely_benign	0.2641	benign	-0.451	Destabilizing	1.0	D	0.687	prob.neutral	D	0.535529459	None	None	N
S/D	0.5126	ambiguous	0.5227	ambiguous	0.452	Stabilizing	0.998	D	0.517	neutral	None	None	None	None	N
S/E	0.6071	likely_pathogenic	0.6258	pathogenic	0.432	Stabilizing	0.992	D	0.497	neutral	None	None	None	None	N
S/F	0.4982	ambiguous	0.5794	pathogenic	-1.024	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
S/G	0.1056	likely_benign	0.1127	benign	-0.951	Destabilizing	0.9	D	0.497	neutral	N	0.502168104	None	None	N
S/H	0.5866	likely_pathogenic	0.6144	pathogenic	-1.358	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
S/I	0.3649	ambiguous	0.4218	ambiguous	-0.288	Destabilizing	0.997	D	0.755	deleterious	D	0.526628689	None	None	N
S/K	0.788	likely_pathogenic	0.8086	pathogenic	-0.406	Destabilizing	0.983	D	0.489	neutral	None	None	None	None	N
S/L	0.1974	likely_benign	0.2424	benign	-0.288	Destabilizing	0.983	D	0.603	neutral	None	None	None	None	N
S/M	0.3368	likely_benign	0.3822	ambiguous	-0.067	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
S/N	0.2118	likely_benign	0.2239	benign	-0.29	Destabilizing	0.999	D	0.549	neutral	D	0.534008522	None	None	N
S/P	0.6281	likely_pathogenic	0.6924	pathogenic	-0.407	Destabilizing	0.998	D	0.705	prob.neutral	None	None	None	None	N
S/Q	0.6376	likely_pathogenic	0.6555	pathogenic	-0.444	Destabilizing	0.999	D	0.585	neutral	None	None	None	None	N
S/R	0.6952	likely_pathogenic	0.7203	pathogenic	-0.343	Destabilizing	0.997	D	0.708	prob.delet.	N	0.508662565	None	None	N
S/T	0.1262	likely_benign	0.1303	benign	-0.438	Destabilizing	0.978	D	0.478	neutral	N	0.486595064	None	None	N
S/V	0.3987	ambiguous	0.4502	ambiguous	-0.407	Destabilizing	0.983	D	0.616	neutral	None	None	None	None	N
S/W	0.6139	likely_pathogenic	0.6634	pathogenic	-0.945	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
S/Y	0.3969	ambiguous	0.456	ambiguous	-0.685	Destabilizing	0.999	D	0.784	deleterious	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.