TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35424	106495;106496;106497	chr2:178530345;178530344;178530343	chr2:179395072;179395071;179395070
N2AB	33783	101572;101573;101574	chr2:178530345;178530344;178530343	chr2:179395072;179395071;179395070
N2A	32856	98791;98792;98793	chr2:178530345;178530344;178530343	chr2:179395072;179395071;179395070
N2B	26359	79300;79301;79302	chr2:178530345;178530344;178530343	chr2:179395072;179395071;179395070
Novex-1	26484	79675;79676;79677	chr2:178530345;178530344;178530343	chr2:179395072;179395071;179395070
Novex-2	26551	79876;79877;79878	chr2:178530345;178530344;178530343	chr2:179395072;179395071;179395070
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-166
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.356
• 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
T/A	None	None	0.979	N	0.306	0.132	0.211220785272	gnomAD-4.0.0	1.20034E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31253E-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	0.0868	likely_benign	0.0884	benign	-0.44	Destabilizing	0.979	D	0.306	neutral	N	0.496002666	None	None	N
T/C	0.577	likely_pathogenic	0.5864	pathogenic	-0.423	Destabilizing	0.999	D	0.682	prob.neutral	None	None	None	None	N
T/D	0.3678	ambiguous	0.3731	ambiguous	0.274	Stabilizing	0.993	D	0.567	neutral	None	None	None	None	N
T/E	0.2758	likely_benign	0.2734	benign	0.221	Stabilizing	0.993	D	0.565	neutral	None	None	None	None	N
T/F	0.2535	likely_benign	0.2594	benign	-0.789	Destabilizing	0.998	D	0.721	prob.delet.	None	None	None	None	N
T/G	0.2884	likely_benign	0.2922	benign	-0.606	Destabilizing	0.993	D	0.547	neutral	None	None	None	None	N
T/H	0.3199	likely_benign	0.3108	benign	-0.822	Destabilizing	0.999	D	0.688	prob.neutral	None	None	None	None	N
T/I	0.1966	likely_benign	0.2087	benign	-0.116	Destabilizing	0.997	D	0.624	neutral	N	0.487383183	None	None	N
T/K	0.2015	likely_benign	0.2006	benign	-0.432	Destabilizing	0.993	D	0.572	neutral	None	None	None	None	N
T/L	0.129	likely_benign	0.1331	benign	-0.116	Destabilizing	0.993	D	0.473	neutral	None	None	None	None	N
T/M	0.1143	likely_benign	0.1192	benign	-0.046	Destabilizing	0.999	D	0.706	prob.neutral	None	None	None	None	N
T/N	0.1381	likely_benign	0.1402	benign	-0.308	Destabilizing	0.991	D	0.519	neutral	N	0.475955468	None	None	N
T/P	0.2322	likely_benign	0.235	benign	-0.193	Destabilizing	0.997	D	0.627	neutral	D	0.523074624	None	None	N
T/Q	0.265	likely_benign	0.2589	benign	-0.496	Destabilizing	0.998	D	0.725	prob.delet.	None	None	None	None	N
T/R	0.1647	likely_benign	0.1649	benign	-0.159	Destabilizing	0.998	D	0.626	neutral	None	None	None	None	N
T/S	0.1217	likely_benign	0.1237	benign	-0.564	Destabilizing	0.979	D	0.396	neutral	N	0.475262034	None	None	N
T/V	0.1821	likely_benign	0.189	benign	-0.193	Destabilizing	0.984	D	0.436	neutral	None	None	None	None	N
T/W	0.5915	likely_pathogenic	0.605	pathogenic	-0.766	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
T/Y	0.3121	likely_benign	0.3201	benign	-0.496	Destabilizing	0.998	D	0.731	prob.delet.	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.