TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31533	94822;94823;94824	chr2:178546831;178546830;178546829	chr2:179411558;179411557;179411556
N2AB	29892	89899;89900;89901	chr2:178546831;178546830;178546829	chr2:179411558;179411557;179411556
N2A	28965	87118;87119;87120	chr2:178546831;178546830;178546829	chr2:179411558;179411557;179411556
N2B	22468	67627;67628;67629	chr2:178546831;178546830;178546829	chr2:179411558;179411557;179411556
Novex-1	22593	68002;68003;68004	chr2:178546831;178546830;178546829	chr2:179411558;179411557;179411556
Novex-2	22660	68203;68204;68205	chr2:178546831;178546830;178546829	chr2:179411558;179411557;179411556
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-118
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.1552
• 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
D/V	None	None	0.978	N	0.673	0.541	0.499473279415	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
D/A	0.8341	likely_pathogenic	0.8903	pathogenic	-0.67	Destabilizing	0.957	D	0.648	neutral	N	0.495691238	None	None	N
D/C	0.9685	likely_pathogenic	0.9821	pathogenic	-0.25	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	N
D/E	0.8337	likely_pathogenic	0.8477	pathogenic	-0.674	Destabilizing	0.039	N	0.316	neutral	N	0.487435578	None	None	N
D/F	0.9807	likely_pathogenic	0.9895	pathogenic	-0.509	Destabilizing	0.999	D	0.649	neutral	None	None	None	None	N
D/G	0.8061	likely_pathogenic	0.87	pathogenic	-0.998	Destabilizing	0.928	D	0.638	neutral	N	0.513670589	None	None	N
D/H	0.8908	likely_pathogenic	0.9213	pathogenic	-0.906	Destabilizing	0.997	D	0.68	prob.neutral	N	0.511264279	None	None	N
D/I	0.9644	likely_pathogenic	0.9765	pathogenic	0.191	Stabilizing	0.992	D	0.662	neutral	None	None	None	None	N
D/K	0.9699	likely_pathogenic	0.9796	pathogenic	-0.434	Destabilizing	0.968	D	0.647	neutral	None	None	None	None	N
D/L	0.9459	likely_pathogenic	0.967	pathogenic	0.191	Stabilizing	0.983	D	0.666	neutral	None	None	None	None	N
D/M	0.9845	likely_pathogenic	0.9894	pathogenic	0.706	Stabilizing	0.999	D	0.651	neutral	None	None	None	None	N
D/N	0.2427	likely_benign	0.2923	benign	-0.786	Destabilizing	0.978	D	0.721	prob.delet.	D	0.522503329	None	None	N
D/P	0.974	likely_pathogenic	0.9787	pathogenic	-0.072	Destabilizing	0.992	D	0.713	prob.delet.	None	None	None	None	N
D/Q	0.941	likely_pathogenic	0.9595	pathogenic	-0.663	Destabilizing	0.968	D	0.773	deleterious	None	None	None	None	N
D/R	0.9593	likely_pathogenic	0.9742	pathogenic	-0.386	Destabilizing	0.983	D	0.697	prob.neutral	None	None	None	None	N
D/S	0.4883	ambiguous	0.5578	ambiguous	-1.05	Destabilizing	0.895	D	0.657	neutral	None	None	None	None	N
D/T	0.7264	likely_pathogenic	0.785	pathogenic	-0.778	Destabilizing	0.983	D	0.723	prob.delet.	None	None	None	None	N
D/V	0.9069	likely_pathogenic	0.9379	pathogenic	-0.072	Destabilizing	0.978	D	0.673	neutral	N	0.518163586	None	None	N
D/W	0.9956	likely_pathogenic	0.9975	pathogenic	-0.383	Destabilizing	0.999	D	0.671	neutral	None	None	None	None	N
D/Y	0.8758	likely_pathogenic	0.9294	pathogenic	-0.288	Destabilizing	0.999	D	0.649	neutral	D	0.540168635	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.