TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6465	19618;19619;19620	chr2:178728533;178728532;178728531	chr2:179593260;179593259;179593258
N2AB	6148	18667;18668;18669	chr2:178728533;178728532;178728531	chr2:179593260;179593259;179593258
N2A	5221	15886;15887;15888	chr2:178728533;178728532;178728531	chr2:179593260;179593259;179593258
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: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-48
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.5351
• 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/N	rs796474434	None	0.98	D	0.531	0.218	0.330589388543	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
S/A	0.0867	likely_benign	0.0879	benign	-0.386	Destabilizing	0.304	N	0.182	neutral	None	None	None	None	N
S/C	0.1292	likely_benign	0.1304	benign	-0.204	Destabilizing	1.0	D	0.612	neutral	N	0.497964596	None	None	N
S/D	0.3818	ambiguous	0.378	ambiguous	-0.124	Destabilizing	0.985	D	0.514	neutral	None	None	None	None	N
S/E	0.4104	ambiguous	0.4029	ambiguous	-0.234	Destabilizing	0.97	D	0.514	neutral	None	None	None	None	N
S/F	0.1351	likely_benign	0.1451	benign	-1.091	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	N
S/G	0.1335	likely_benign	0.1281	benign	-0.456	Destabilizing	0.925	D	0.461	neutral	N	0.494975628	None	None	N
S/H	0.2973	likely_benign	0.2995	benign	-1.025	Destabilizing	1.0	D	0.594	neutral	None	None	None	None	N
S/I	0.1265	likely_benign	0.1175	benign	-0.33	Destabilizing	0.994	D	0.679	prob.neutral	N	0.485367296	None	None	N
S/K	0.5681	likely_pathogenic	0.5493	ambiguous	-0.396	Destabilizing	0.942	D	0.495	neutral	None	None	None	None	N
S/L	0.1032	likely_benign	0.0974	benign	-0.33	Destabilizing	0.97	D	0.622	neutral	None	None	None	None	N
S/M	0.1788	likely_benign	0.1842	benign	0.079	Stabilizing	1.0	D	0.595	neutral	None	None	None	None	N
S/N	0.1331	likely_benign	0.129	benign	-0.104	Destabilizing	0.98	D	0.531	neutral	D	0.529557879	None	None	N
S/P	0.7403	likely_pathogenic	0.7015	pathogenic	-0.323	Destabilizing	0.996	D	0.59	neutral	None	None	None	None	N
S/Q	0.4083	ambiguous	0.3938	ambiguous	-0.445	Destabilizing	0.991	D	0.541	neutral	None	None	None	None	N
S/R	0.4711	ambiguous	0.4344	ambiguous	-0.152	Destabilizing	0.151	N	0.311	neutral	N	0.483150799	None	None	N
S/T	0.0769	likely_benign	0.0802	benign	-0.214	Destabilizing	0.961	D	0.491	neutral	N	0.518532809	None	None	N
S/V	0.1339	likely_benign	0.1346	benign	-0.323	Destabilizing	0.991	D	0.597	neutral	None	None	None	None	N
S/W	0.3176	likely_benign	0.3162	benign	-1.085	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
S/Y	0.1594	likely_benign	0.1587	benign	-0.803	Destabilizing	0.999	D	0.689	prob.neutral	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.