TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26293	79102;79103;79104	chr2:178567255;178567254;178567253	chr2:179431982;179431981;179431980
N2AB	24652	74179;74180;74181	chr2:178567255;178567254;178567253	chr2:179431982;179431981;179431980
N2A	23725	71398;71399;71400	chr2:178567255;178567254;178567253	chr2:179431982;179431981;179431980
N2B	17228	51907;51908;51909	chr2:178567255;178567254;178567253	chr2:179431982;179431981;179431980
Novex-1	17353	52282;52283;52284	chr2:178567255;178567254;178567253	chr2:179431982;179431981;179431980
Novex-2	17420	52483;52484;52485	chr2:178567255;178567254;178567253	chr2:179431982;179431981;179431980
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: Fn3-79
• Domain position: 8
• Structural Position: 8
• Q(SASA): 0.1991
• 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	None	None	0.994	N	0.754	0.272	0.394536629495	gnomAD-4.0.0	1.60906E-06	None	None	None	None	N	None	0	2.32829E-05	None	0	0	None	0	0	0	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
P/A	0.164	likely_benign	0.2079	benign	-0.417	Destabilizing	0.958	D	0.595	neutral	N	0.486777241	None	None	N
P/C	0.6479	likely_pathogenic	0.6975	pathogenic	-0.786	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
P/D	0.5679	likely_pathogenic	0.6193	pathogenic	-0.242	Destabilizing	0.998	D	0.803	deleterious	None	None	None	None	N
P/E	0.4158	ambiguous	0.4821	ambiguous	-0.348	Destabilizing	0.995	D	0.793	deleterious	None	None	None	None	N
P/F	0.6617	likely_pathogenic	0.7214	pathogenic	-0.619	Destabilizing	0.998	D	0.905	deleterious	None	None	None	None	N
P/G	0.532	ambiguous	0.5794	pathogenic	-0.527	Destabilizing	0.995	D	0.801	deleterious	None	None	None	None	N
P/H	0.3848	ambiguous	0.4459	ambiguous	-0.052	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
P/I	0.4537	ambiguous	0.5326	ambiguous	-0.274	Destabilizing	0.982	D	0.827	deleterious	None	None	None	None	N
P/K	0.4485	ambiguous	0.5332	ambiguous	-0.46	Destabilizing	0.995	D	0.789	deleterious	None	None	None	None	N
P/L	0.2123	likely_benign	0.2656	benign	-0.274	Destabilizing	0.142	N	0.57	neutral	N	0.521105512	None	None	N
P/M	0.4279	ambiguous	0.4845	ambiguous	-0.516	Destabilizing	0.998	D	0.882	deleterious	None	None	None	None	N
P/N	0.4874	ambiguous	0.5429	ambiguous	-0.276	Destabilizing	0.998	D	0.891	deleterious	None	None	None	None	N
P/Q	0.3129	likely_benign	0.3812	ambiguous	-0.483	Destabilizing	0.998	D	0.847	deleterious	N	0.487132863	None	None	N
P/R	0.3543	ambiguous	0.4265	ambiguous	0.019	Stabilizing	0.994	D	0.889	deleterious	N	0.516339934	None	None	N
P/S	0.2827	likely_benign	0.3414	ambiguous	-0.623	Destabilizing	0.994	D	0.754	deleterious	N	0.467863292	None	None	N
P/T	0.204	likely_benign	0.2485	benign	-0.629	Destabilizing	0.988	D	0.724	prob.delet.	N	0.496665516	None	None	N
P/V	0.3261	likely_benign	0.3873	ambiguous	-0.289	Destabilizing	0.982	D	0.731	prob.delet.	None	None	None	None	N
P/W	0.8457	likely_pathogenic	0.8731	pathogenic	-0.688	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
P/Y	0.6773	likely_pathogenic	0.7359	pathogenic	-0.408	Destabilizing	0.999	D	0.894	deleterious	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.