TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29900	89923;89924;89925	chr2:178553202;178553201;178553200	chr2:179417929;179417928;179417927
N2AB	28259	85000;85001;85002	chr2:178553202;178553201;178553200	chr2:179417929;179417928;179417927
N2A	27332	82219;82220;82221	chr2:178553202;178553201;178553200	chr2:179417929;179417928;179417927
N2B	20835	62728;62729;62730	chr2:178553202;178553201;178553200	chr2:179417929;179417928;179417927
Novex-1	20960	63103;63104;63105	chr2:178553202;178553201;178553200	chr2:179417929;179417928;179417927
Novex-2	21027	63304;63305;63306	chr2:178553202;178553201;178553200	chr2:179417929;179417928;179417927
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-147
• Domain position: 59
• Structural Position: 141
• Q(SASA): 0.3214
• 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/L	rs1302918553	-0.734	0.032	N	0.459	0.229	0.516162830352	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.66E-05	0
P/L	rs1302918553	-0.734	0.032	N	0.459	0.229	0.516162830352	gnomAD-4.0.0	8.21064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.89388E-06	0	1.6564E-05
P/R	None	None	0.971	N	0.669	0.281	0.478527412683	gnomAD-4.0.0	6.8422E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15937E-05	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	0.117	likely_benign	0.1005	benign	-1.567	Destabilizing	0.698	D	0.468	neutral	N	0.503792643	None	None	N
P/C	0.4964	ambiguous	0.4333	ambiguous	-1.177	Destabilizing	0.998	D	0.691	prob.neutral	None	None	None	None	N
P/D	0.517	ambiguous	0.4698	ambiguous	-1.358	Destabilizing	0.956	D	0.574	neutral	None	None	None	None	N
P/E	0.3197	likely_benign	0.2893	benign	-1.356	Destabilizing	0.956	D	0.567	neutral	None	None	None	None	N
P/F	0.5411	ambiguous	0.476	ambiguous	-1.249	Destabilizing	0.915	D	0.718	prob.delet.	None	None	None	None	N
P/G	0.3089	likely_benign	0.2717	benign	-1.892	Destabilizing	0.86	D	0.564	neutral	None	None	None	None	N
P/H	0.1908	likely_benign	0.1673	benign	-1.4	Destabilizing	0.997	D	0.636	neutral	D	0.527997654	None	None	N
P/I	0.3928	ambiguous	0.3434	ambiguous	-0.771	Destabilizing	0.915	D	0.707	prob.neutral	None	None	None	None	N
P/K	0.2306	likely_benign	0.2025	benign	-1.305	Destabilizing	0.956	D	0.568	neutral	None	None	None	None	N
P/L	0.1433	likely_benign	0.1273	benign	-0.771	Destabilizing	0.032	N	0.459	neutral	N	0.508083742	None	None	N
P/M	0.3853	ambiguous	0.3292	benign	-0.601	Destabilizing	0.988	D	0.651	neutral	None	None	None	None	N
P/N	0.327	likely_benign	0.2839	benign	-1.122	Destabilizing	0.956	D	0.667	neutral	None	None	None	None	N
P/Q	0.1629	likely_benign	0.1446	benign	-1.294	Destabilizing	0.978	D	0.641	neutral	None	None	None	None	N
P/R	0.1525	likely_benign	0.132	benign	-0.775	Destabilizing	0.971	D	0.669	neutral	N	0.479107629	None	None	N
P/S	0.137	likely_benign	0.1205	benign	-1.683	Destabilizing	0.294	N	0.287	neutral	N	0.462714025	None	None	N
P/T	0.1295	likely_benign	0.1138	benign	-1.566	Destabilizing	0.698	D	0.517	neutral	N	0.493999724	None	None	N
P/V	0.2797	likely_benign	0.2438	benign	-1.001	Destabilizing	0.754	D	0.58	neutral	None	None	None	None	N
P/W	0.6669	likely_pathogenic	0.5978	pathogenic	-1.423	Destabilizing	0.998	D	0.682	prob.neutral	None	None	None	None	N
P/Y	0.4776	ambiguous	0.4042	ambiguous	-1.135	Destabilizing	0.978	D	0.713	prob.delet.	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.