TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16731	50416;50417;50418	chr2:178612334;178612333;178612332	chr2:179477061;179477060;179477059
N2AB	15090	45493;45494;45495	chr2:178612334;178612333;178612332	chr2:179477061;179477060;179477059
N2A	14163	42712;42713;42714	chr2:178612334;178612333;178612332	chr2:179477061;179477060;179477059
N2B	7666	23221;23222;23223	chr2:178612334;178612333;178612332	chr2:179477061;179477060;179477059
Novex-1	7791	23596;23597;23598	chr2:178612334;178612333;178612332	chr2:179477061;179477060;179477059
Novex-2	7858	23797;23798;23799	chr2:178612334;178612333;178612332	chr2:179477061;179477060;179477059
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-9
• Domain position: 81
• Structural Position: 114
• Q(SASA): 0.4957
• Predicted PPI site: I

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	None	None	0.549	N	0.362	0.225	0.511162291539	gnomAD-4.0.0	1.59386E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86236E-06	0	0
I/V	None	None	0.001	N	0.172	0.072	0.148003135375	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
I/A	0.3001	likely_benign	0.3361	benign	-0.42	Destabilizing	0.002	N	0.195	neutral	None	None	None	None	I
I/C	0.7794	likely_pathogenic	0.835	pathogenic	-0.644	Destabilizing	0.977	D	0.436	neutral	None	None	None	None	I
I/D	0.9495	likely_pathogenic	0.9763	pathogenic	-0.024	Destabilizing	0.92	D	0.563	neutral	None	None	None	None	I
I/E	0.8677	likely_pathogenic	0.9329	pathogenic	-0.126	Destabilizing	0.85	D	0.537	neutral	None	None	None	None	I
I/F	0.361	ambiguous	0.4582	ambiguous	-0.537	Destabilizing	0.85	D	0.355	neutral	None	None	None	None	I
I/G	0.8734	likely_pathogenic	0.8987	pathogenic	-0.546	Destabilizing	0.447	N	0.552	neutral	None	None	None	None	I
I/H	0.8549	likely_pathogenic	0.931	pathogenic	0.14	Stabilizing	0.992	D	0.545	neutral	None	None	None	None	I
I/K	0.8105	likely_pathogenic	0.8983	pathogenic	-0.17	Destabilizing	0.81	D	0.547	neutral	N	0.476884585	None	None	I
I/L	0.2135	likely_benign	0.2405	benign	-0.222	Destabilizing	0.099	N	0.267	neutral	N	0.46089094	None	None	I
I/M	0.2004	likely_benign	0.2422	benign	-0.343	Destabilizing	0.81	D	0.365	neutral	N	0.481849883	None	None	I
I/N	0.6579	likely_pathogenic	0.798	pathogenic	-0.011	Destabilizing	0.92	D	0.557	neutral	None	None	None	None	I
I/P	0.9563	likely_pathogenic	0.9636	pathogenic	-0.256	Destabilizing	0.92	D	0.559	neutral	None	None	None	None	I
I/Q	0.7895	likely_pathogenic	0.8797	pathogenic	-0.231	Destabilizing	0.92	D	0.555	neutral	None	None	None	None	I
I/R	0.7054	likely_pathogenic	0.8251	pathogenic	0.35	Stabilizing	0.896	D	0.558	neutral	N	0.478022934	None	None	I
I/S	0.4728	ambiguous	0.5944	pathogenic	-0.453	Destabilizing	0.447	N	0.485	neutral	None	None	None	None	I
I/T	0.1946	likely_benign	0.3223	benign	-0.447	Destabilizing	0.549	D	0.362	neutral	N	0.478238961	None	None	I
I/V	0.066	likely_benign	0.0719	benign	-0.256	Destabilizing	0.001	N	0.172	neutral	N	0.374105953	None	None	I
I/W	0.9372	likely_pathogenic	0.9663	pathogenic	-0.545	Destabilizing	0.992	D	0.633	neutral	None	None	None	None	I
I/Y	0.8241	likely_pathogenic	0.8852	pathogenic	-0.283	Destabilizing	0.92	D	0.447	neutral	None	None	None	None	I

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.