TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24840	74743;74744;74745	chr2:178571614;178571613;178571612	chr2:179436341;179436340;179436339
N2AB	23199	69820;69821;69822	chr2:178571614;178571613;178571612	chr2:179436341;179436340;179436339
N2A	22272	67039;67040;67041	chr2:178571614;178571613;178571612	chr2:179436341;179436340;179436339
N2B	15775	47548;47549;47550	chr2:178571614;178571613;178571612	chr2:179436341;179436340;179436339
Novex-1	15900	47923;47924;47925	chr2:178571614;178571613;178571612	chr2:179436341;179436340;179436339
Novex-2	15967	48124;48125;48126	chr2:178571614;178571613;178571612	chr2:179436341;179436340;179436339
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: Fn3-68
• Domain position: 33
• Structural Position: 34
• Q(SASA): 0.7272
• 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
S/P	None	None	0.007	N	0.172	0.248	0.112648838833	gnomAD-4.0.0	1.59247E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.88587E-05	0	0	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	0.0717	likely_benign	0.0702	benign	-0.481	Destabilizing	0.012	N	0.059	neutral	N	0.400827699	None	None	I
S/C	0.0974	likely_benign	0.0929	benign	-0.213	Destabilizing	0.994	D	0.422	neutral	N	0.472725138	None	None	I
S/D	0.555	ambiguous	0.5463	ambiguous	0.09	Stabilizing	0.742	D	0.294	neutral	None	None	None	None	I
S/E	0.6488	likely_pathogenic	0.6319	pathogenic	-0.013	Destabilizing	0.373	N	0.337	neutral	None	None	None	None	I
S/F	0.2555	likely_benign	0.2319	benign	-1.151	Destabilizing	0.979	D	0.485	neutral	N	0.515788	None	None	I
S/G	0.1012	likely_benign	0.0949	benign	-0.57	Destabilizing	0.543	D	0.357	neutral	None	None	None	None	I
S/H	0.3988	ambiguous	0.3741	ambiguous	-1.132	Destabilizing	0.953	D	0.436	neutral	None	None	None	None	I
S/I	0.1676	likely_benign	0.1517	benign	-0.372	Destabilizing	0.953	D	0.469	neutral	None	None	None	None	I
S/K	0.7576	likely_pathogenic	0.7315	pathogenic	-0.41	Destabilizing	0.59	D	0.288	neutral	None	None	None	None	I
S/L	0.1032	likely_benign	0.0951	benign	-0.372	Destabilizing	0.742	D	0.455	neutral	None	None	None	None	I
S/M	0.184	likely_benign	0.1646	benign	0.044	Stabilizing	0.953	D	0.436	neutral	None	None	None	None	I
S/N	0.1361	likely_benign	0.1265	benign	-0.114	Destabilizing	0.742	D	0.364	neutral	None	None	None	None	I
S/P	0.1151	likely_benign	0.1109	benign	-0.381	Destabilizing	0.007	N	0.172	neutral	N	0.352975037	None	None	I
S/Q	0.4922	ambiguous	0.455	ambiguous	-0.417	Destabilizing	0.037	N	0.087	neutral	None	None	None	None	I
S/R	0.7297	likely_pathogenic	0.7	pathogenic	-0.199	Destabilizing	0.59	D	0.441	neutral	None	None	None	None	I
S/T	0.0867	likely_benign	0.0803	benign	-0.245	Destabilizing	0.472	N	0.347	neutral	N	0.433689479	None	None	I
S/V	0.1554	likely_benign	0.1397	benign	-0.381	Destabilizing	0.742	D	0.471	neutral	None	None	None	None	I
S/W	0.461	ambiguous	0.4303	ambiguous	-1.131	Destabilizing	0.996	D	0.508	neutral	None	None	None	None	I
S/Y	0.2647	likely_benign	0.2458	benign	-0.855	Destabilizing	0.979	D	0.493	neutral	N	0.472218159	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.