TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7105	21538;21539;21540	chr2:178723946;178723945;178723944	chr2:179588673;179588672;179588671
N2AB	6788	20587;20588;20589	chr2:178723946;178723945;178723944	chr2:179588673;179588672;179588671
N2A	5861	17806;17807;17808	chr2:178723946;178723945;178723944	chr2:179588673;179588672;179588671
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-55
• Domain position: 62
• Structural Position: 143
• Q(SASA): 0.3505
• 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
S/Y	None	None	0.272	N	0.491	0.176	0.337378238328	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	3.66327E-05

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
S/A	0.0732	likely_benign	0.0726	benign	-0.551	Destabilizing	0.081	N	0.337	neutral	N	0.477181179	None	None	N
S/C	0.1188	likely_benign	0.1111	benign	-0.259	Destabilizing	0.002	N	0.259	neutral	N	0.47509027	None	None	N
S/D	0.1803	likely_benign	0.172	benign	-0.183	Destabilizing	0.001	N	0.136	neutral	None	None	None	None	N
S/E	0.3002	likely_benign	0.2898	benign	-0.262	Destabilizing	0.124	N	0.309	neutral	None	None	None	None	N
S/F	0.1101	likely_benign	0.1057	benign	-1.147	Destabilizing	0.002	N	0.302	neutral	N	0.47483678	None	None	N
S/G	0.0878	likely_benign	0.0853	benign	-0.683	Destabilizing	0.055	N	0.345	neutral	None	None	None	None	N
S/H	0.195	likely_benign	0.1796	benign	-1.296	Destabilizing	0.667	D	0.429	neutral	None	None	None	None	N
S/I	0.1382	likely_benign	0.1274	benign	-0.324	Destabilizing	0.124	N	0.473	neutral	None	None	None	None	N
S/K	0.3991	ambiguous	0.371	ambiguous	-0.498	Destabilizing	0.22	N	0.32	neutral	None	None	None	None	N
S/L	0.0836	likely_benign	0.0834	benign	-0.324	Destabilizing	0.055	N	0.473	neutral	None	None	None	None	N
S/M	0.1624	likely_benign	0.1555	benign	0.192	Stabilizing	0.667	D	0.422	neutral	None	None	None	None	N
S/N	0.1009	likely_benign	0.094	benign	-0.281	Destabilizing	None	N	0.109	neutral	None	None	None	None	N
S/P	0.3967	ambiguous	0.3799	ambiguous	-0.371	Destabilizing	0.822	D	0.453	neutral	N	0.492265275	None	None	N
S/Q	0.3207	likely_benign	0.2992	benign	-0.602	Destabilizing	0.667	D	0.383	neutral	None	None	None	None	N
S/R	0.2982	likely_benign	0.2786	benign	-0.277	Destabilizing	0.497	N	0.471	neutral	None	None	None	None	N
S/T	0.0837	likely_benign	0.0815	benign	-0.372	Destabilizing	0.003	N	0.143	neutral	N	0.450322652	None	None	N
S/V	0.1408	likely_benign	0.1325	benign	-0.371	Destabilizing	0.124	N	0.487	neutral	None	None	None	None	N
S/W	0.2039	likely_benign	0.2001	benign	-1.112	Destabilizing	0.883	D	0.474	neutral	None	None	None	None	N
S/Y	0.0984	likely_benign	0.0931	benign	-0.837	Destabilizing	0.272	N	0.491	neutral	N	0.4661895	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.