TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21497	64714;64715;64716	chr2:178585255;178585254;178585253	chr2:179449982;179449981;179449980
N2AB	19856	59791;59792;59793	chr2:178585255;178585254;178585253	chr2:179449982;179449981;179449980
N2A	18929	57010;57011;57012	chr2:178585255;178585254;178585253	chr2:179449982;179449981;179449980
N2B	12432	37519;37520;37521	chr2:178585255;178585254;178585253	chr2:179449982;179449981;179449980
Novex-1	12557	37894;37895;37896	chr2:178585255;178585254;178585253	chr2:179449982;179449981;179449980
Novex-2	12624	38095;38096;38097	chr2:178585255;178585254;178585253	chr2:179449982;179449981;179449980
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-124
• Domain position: 29
• Structural Position: 45
• Q(SASA): 0.5691
• 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
T/I	rs1236376736	0.192	None	N	0.118	0.143	0.0954503805726	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
T/I	rs1236376736	0.192	None	N	0.118	0.143	0.0954503805726	gnomAD-4.0.0	1.36883E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79943E-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
T/A	0.0618	likely_benign	0.0637	benign	-0.315	Destabilizing	0.003	N	0.239	neutral	N	0.484785595	None	None	I
T/C	0.2577	likely_benign	0.2707	benign	-0.098	Destabilizing	0.245	N	0.455	neutral	None	None	None	None	I
T/D	0.2523	likely_benign	0.2406	benign	-0.118	Destabilizing	0.044	N	0.441	neutral	None	None	None	None	I
T/E	0.1963	likely_benign	0.1898	benign	-0.185	Destabilizing	0.009	N	0.373	neutral	None	None	None	None	I
T/F	0.1101	likely_benign	0.1074	benign	-0.665	Destabilizing	None	N	0.195	neutral	None	None	None	None	I
T/G	0.1618	likely_benign	0.1641	benign	-0.478	Destabilizing	0.037	N	0.393	neutral	None	None	None	None	I
T/H	0.1496	likely_benign	0.1462	benign	-0.765	Destabilizing	0.245	N	0.499	neutral	None	None	None	None	I
T/I	0.0559	likely_benign	0.0553	benign	0.004	Stabilizing	None	N	0.118	neutral	N	0.521303755	None	None	I
T/K	0.1378	likely_benign	0.1285	benign	-0.483	Destabilizing	0.009	N	0.378	neutral	None	None	None	None	I
T/L	0.0565	likely_benign	0.0547	benign	0.004	Stabilizing	None	N	0.119	neutral	None	None	None	None	I
T/M	0.0752	likely_benign	0.0756	benign	0.188	Stabilizing	0.001	N	0.261	neutral	None	None	None	None	I
T/N	0.0861	likely_benign	0.0866	benign	-0.147	Destabilizing	0.065	N	0.337	neutral	N	0.495194589	None	None	I
T/P	0.3032	likely_benign	0.279	benign	-0.073	Destabilizing	0.065	N	0.495	neutral	N	0.501065241	None	None	I
T/Q	0.1454	likely_benign	0.1446	benign	-0.391	Destabilizing	0.002	N	0.228	neutral	None	None	None	None	I
T/R	0.1305	likely_benign	0.1198	benign	-0.165	Destabilizing	0.044	N	0.449	neutral	None	None	None	None	I
T/S	0.0732	likely_benign	0.0753	benign	-0.321	Destabilizing	0.014	N	0.304	neutral	N	0.482358578	None	None	I
T/V	0.0532	likely_benign	0.0532	benign	-0.073	Destabilizing	None	N	0.071	neutral	None	None	None	None	I
T/W	0.475	ambiguous	0.4519	ambiguous	-0.685	Destabilizing	0.788	D	0.488	neutral	None	None	None	None	I
T/Y	0.1763	likely_benign	0.1775	benign	-0.428	Destabilizing	0.022	N	0.492	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.