TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8199	24820;24821;24822	chr2:178718511;178718510;178718509	chr2:179583238;179583237;179583236
N2AB	7882	23869;23870;23871	chr2:178718511;178718510;178718509	chr2:179583238;179583237;179583236
N2A	6955	21088;21089;21090	chr2:178718511;178718510;178718509	chr2:179583238;179583237;179583236
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: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-67
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.5707
• 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	rs1438804317	None	0.27	D	0.393	0.202	0.274366138417	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	4.79386E-04
P/S	rs1438804317	None	0.27	D	0.393	0.202	0.274366138417	gnomAD-4.0.0	4.33807E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.08578E-06	0	1.60159E-05

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	0.0772	likely_benign	0.0877	benign	-0.433	Destabilizing	0.27	N	0.407	neutral	D	0.528728373	None	None	N
P/C	0.5255	ambiguous	0.5307	ambiguous	-0.673	Destabilizing	0.995	D	0.489	neutral	None	None	None	None	N
P/D	0.3054	likely_benign	0.4031	ambiguous	-0.419	Destabilizing	0.543	D	0.383	neutral	None	None	None	None	N
P/E	0.1999	likely_benign	0.2638	benign	-0.539	Destabilizing	0.031	N	0.281	neutral	None	None	None	None	N
P/F	0.4168	ambiguous	0.4892	ambiguous	-0.716	Destabilizing	0.944	D	0.492	neutral	None	None	None	None	N
P/G	0.3011	likely_benign	0.3464	ambiguous	-0.54	Destabilizing	0.704	D	0.458	neutral	None	None	None	None	N
P/H	0.179	likely_benign	0.219	benign	-0.147	Destabilizing	0.944	D	0.486	neutral	None	None	None	None	N
P/I	0.2698	likely_benign	0.3277	benign	-0.303	Destabilizing	0.031	N	0.399	neutral	None	None	None	None	N
P/K	0.2253	likely_benign	0.2761	benign	-0.491	Destabilizing	0.013	N	0.215	neutral	None	None	None	None	N
P/L	0.1186	likely_benign	0.14	benign	-0.303	Destabilizing	0.27	N	0.477	neutral	N	0.510836045	None	None	N
P/M	0.2752	likely_benign	0.3189	benign	-0.444	Destabilizing	0.944	D	0.484	neutral	None	None	None	None	N
P/N	0.2601	likely_benign	0.3254	benign	-0.233	Destabilizing	0.031	N	0.352	neutral	None	None	None	None	N
P/Q	0.1328	likely_benign	0.1596	benign	-0.477	Destabilizing	0.642	D	0.408	neutral	N	0.48777947	None	None	N
P/R	0.1567	likely_benign	0.1884	benign	0.021	Stabilizing	0.473	N	0.473	neutral	N	0.510836045	None	None	N
P/S	0.113	likely_benign	0.1347	benign	-0.54	Destabilizing	0.27	N	0.393	neutral	D	0.527824296	None	None	N
P/T	0.1003	likely_benign	0.122	benign	-0.563	Destabilizing	0.023	N	0.269	neutral	N	0.501003054	None	None	N
P/V	0.1833	likely_benign	0.2134	benign	-0.313	Destabilizing	0.329	N	0.455	neutral	None	None	None	None	N
P/W	0.6308	likely_pathogenic	0.6872	pathogenic	-0.794	Destabilizing	0.995	D	0.524	neutral	None	None	None	None	N
P/Y	0.4066	ambiguous	0.4655	ambiguous	-0.505	Destabilizing	0.981	D	0.493	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.