TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8644	26155;26156;26157	chr2:178715256;178715255;178715254	chr2:179579983;179579982;179579981
N2AB	8327	25204;25205;25206	chr2:178715256;178715255;178715254	chr2:179579983;179579982;179579981
N2A	7400	22423;22424;22425	chr2:178715256;178715255;178715254	chr2:179579983;179579982;179579981
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-72
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.2975
• 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
I/T	rs779643078	-1.371	None	N	0.202	0.077	0.299427821978	gnomAD-2.1.1	4.18E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.56E-05	None	0	0	0
I/T	rs779643078	-1.371	None	N	0.202	0.077	0.299427821978	gnomAD-4.0.0	1.62272E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4821E-05	0
I/V	rs2077304950	None	None	N	0.067	0.172	0.0806252709748	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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
I/A	0.1282	likely_benign	0.1141	benign	-1.269	Destabilizing	None	N	0.189	neutral	None	None	None	None	N
I/C	0.4182	ambiguous	0.4026	ambiguous	-0.853	Destabilizing	0.245	N	0.409	neutral	None	None	None	None	N
I/D	0.3207	likely_benign	0.2956	benign	-0.464	Destabilizing	0.044	N	0.455	neutral	None	None	None	None	N
I/E	0.2617	likely_benign	0.2353	benign	-0.448	Destabilizing	0.009	N	0.397	neutral	None	None	None	None	N
I/F	0.1013	likely_benign	0.0942	benign	-0.724	Destabilizing	0.017	N	0.329	neutral	N	0.445304487	None	None	N
I/G	0.2915	likely_benign	0.2591	benign	-1.585	Destabilizing	0.009	N	0.307	neutral	None	None	None	None	N
I/H	0.2031	likely_benign	0.1809	benign	-0.667	Destabilizing	0.245	N	0.477	neutral	None	None	None	None	N
I/K	0.1601	likely_benign	0.14	benign	-0.819	Destabilizing	0.009	N	0.371	neutral	None	None	None	None	N
I/L	0.0783	likely_benign	0.0755	benign	-0.485	Destabilizing	None	N	0.066	neutral	N	0.453307894	None	None	N
I/M	0.0889	likely_benign	0.0808	benign	-0.517	Destabilizing	None	N	0.217	neutral	N	0.466410478	None	None	N
I/N	0.1071	likely_benign	0.1053	benign	-0.71	Destabilizing	0.017	N	0.498	neutral	N	0.442186824	None	None	N
I/P	0.8442	likely_pathogenic	0.8249	pathogenic	-0.714	Destabilizing	0.044	N	0.513	neutral	None	None	None	None	N
I/Q	0.1757	likely_benign	0.1515	benign	-0.819	Destabilizing	0.044	N	0.558	neutral	None	None	None	None	N
I/R	0.1112	likely_benign	0.0992	benign	-0.3	Destabilizing	0.044	N	0.539	neutral	None	None	None	None	N
I/S	0.1006	likely_benign	0.0938	benign	-1.344	Destabilizing	None	N	0.243	neutral	N	0.358453506	None	None	N
I/T	0.0941	likely_benign	0.0872	benign	-1.202	Destabilizing	None	N	0.202	neutral	N	0.413653428	None	None	N
I/V	0.0549	likely_benign	0.0542	benign	-0.714	Destabilizing	None	N	0.067	neutral	N	0.357221355	None	None	N
I/W	0.6234	likely_pathogenic	0.5752	pathogenic	-0.786	Destabilizing	0.788	D	0.484	neutral	None	None	None	None	N
I/Y	0.2861	likely_benign	0.2666	benign	-0.554	Destabilizing	0.085	N	0.539	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.