TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34316	103171;103172;103173	chr2:178533669;178533668;178533667	chr2:179398396;179398395;179398394
N2AB	32675	98248;98249;98250	chr2:178533669;178533668;178533667	chr2:179398396;179398395;179398394
N2A	31748	95467;95468;95469	chr2:178533669;178533668;178533667	chr2:179398396;179398395;179398394
N2B	25251	75976;75977;75978	chr2:178533669;178533668;178533667	chr2:179398396;179398395;179398394
Novex-1	25376	76351;76352;76353	chr2:178533669;178533668;178533667	chr2:179398396;179398395;179398394
Novex-2	25443	76552;76553;76554	chr2:178533669;178533668;178533667	chr2:179398396;179398395;179398394
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-161
• Domain position: 59
• Structural Position: 136
• Q(SASA): 0.0953
• 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
Y/C	rs1406877841	None	0.1	N	0.611	0.263	0.21737058555	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
Y/C	rs1406877841	None	0.1	N	0.611	0.263	0.21737058555	gnomAD-4.0.0	6.56996E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46985E-05	0	0
Y/H	None	None	0.997	N	0.76	0.442	0.225215365344	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
Y/A	0.9681	likely_pathogenic	0.9753	pathogenic	-2.814	Highly Destabilizing	0.91	D	0.601	neutral	None	None	None	None	N
Y/C	0.5424	ambiguous	0.6298	pathogenic	-1.804	Destabilizing	0.1	N	0.611	neutral	N	0.404997715	None	None	N
Y/D	0.972	likely_pathogenic	0.9813	pathogenic	-2.427	Highly Destabilizing	0.997	D	0.813	deleterious	N	0.450558374	None	None	N
Y/E	0.9877	likely_pathogenic	0.9918	pathogenic	-2.235	Highly Destabilizing	0.998	D	0.764	deleterious	None	None	None	None	N
Y/F	0.1956	likely_benign	0.2076	benign	-0.943	Destabilizing	0.99	D	0.619	neutral	N	0.489170962	None	None	N
Y/G	0.9653	likely_pathogenic	0.9732	pathogenic	-3.239	Highly Destabilizing	0.993	D	0.759	deleterious	None	None	None	None	N
Y/H	0.5276	ambiguous	0.6331	pathogenic	-1.703	Destabilizing	0.997	D	0.76	deleterious	N	0.44649762	None	None	N
Y/I	0.9162	likely_pathogenic	0.927	pathogenic	-1.437	Destabilizing	0.986	D	0.721	prob.delet.	None	None	None	None	N
Y/K	0.9709	likely_pathogenic	0.9815	pathogenic	-1.948	Destabilizing	0.998	D	0.758	deleterious	None	None	None	None	N
Y/L	0.8378	likely_pathogenic	0.8593	pathogenic	-1.437	Destabilizing	0.91	D	0.6	neutral	None	None	None	None	N
Y/M	0.952	likely_pathogenic	0.9575	pathogenic	-1.279	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
Y/N	0.8606	likely_pathogenic	0.8975	pathogenic	-2.614	Highly Destabilizing	0.997	D	0.791	deleterious	N	0.48039955	None	None	N
Y/P	0.9966	likely_pathogenic	0.9974	pathogenic	-1.905	Destabilizing	0.998	D	0.821	deleterious	None	None	None	None	N
Y/Q	0.9453	likely_pathogenic	0.9651	pathogenic	-2.369	Highly Destabilizing	0.998	D	0.78	deleterious	None	None	None	None	N
Y/R	0.9039	likely_pathogenic	0.9364	pathogenic	-1.703	Destabilizing	0.998	D	0.797	deleterious	None	None	None	None	N
Y/S	0.8534	likely_pathogenic	0.8922	pathogenic	-3.127	Highly Destabilizing	0.982	D	0.699	prob.neutral	N	0.462733722	None	None	N
Y/T	0.9594	likely_pathogenic	0.9674	pathogenic	-2.812	Highly Destabilizing	0.986	D	0.719	prob.delet.	None	None	None	None	N
Y/V	0.8735	likely_pathogenic	0.8932	pathogenic	-1.905	Destabilizing	0.953	D	0.653	neutral	None	None	None	None	N
Y/W	0.6032	likely_pathogenic	0.6567	pathogenic	-0.264	Destabilizing	0.999	D	0.751	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.