TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20042	60349;60350;60351	chr2:178591695;178591694;178591693	chr2:179456422;179456421;179456420
N2AB	18401	55426;55427;55428	chr2:178591695;178591694;178591693	chr2:179456422;179456421;179456420
N2A	17474	52645;52646;52647	chr2:178591695;178591694;178591693	chr2:179456422;179456421;179456420
N2B	10977	33154;33155;33156	chr2:178591695;178591694;178591693	chr2:179456422;179456421;179456420
Novex-1	11102	33529;33530;33531	chr2:178591695;178591694;178591693	chr2:179456422;179456421;179456420
Novex-2	11169	33730;33731;33732	chr2:178591695;178591694;178591693	chr2:179456422;179456421;179456420
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Fn3-33
• Domain position: 66
• Structural Position: 99
• Q(SASA): 0.3819
• 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
Q/H	None	None	0.006	N	0.189	0.136	0.321951552304	gnomAD-4.0.0	1.59198E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43316E-05	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
Q/A	0.1682	likely_benign	0.1484	benign	-0.273	Destabilizing	0.495	N	0.313	neutral	None	None	None	None	N
Q/C	0.74	likely_pathogenic	0.7304	pathogenic	0.242	Stabilizing	0.995	D	0.367	neutral	None	None	None	None	N
Q/D	0.4311	ambiguous	0.456	ambiguous	-0.085	Destabilizing	0.003	N	0.075	neutral	None	None	None	None	N
Q/E	0.0655	likely_benign	0.0658	benign	-0.107	Destabilizing	0.003	N	0.043	neutral	N	0.324385713	None	None	N
Q/F	0.8051	likely_pathogenic	0.7926	pathogenic	-0.415	Destabilizing	0.944	D	0.405	neutral	None	None	None	None	N
Q/G	0.3385	likely_benign	0.3126	benign	-0.483	Destabilizing	0.495	N	0.299	neutral	None	None	None	None	N
Q/H	0.2869	likely_benign	0.2766	benign	-0.424	Destabilizing	0.006	N	0.189	neutral	N	0.455392902	None	None	N
Q/I	0.4519	ambiguous	0.4288	ambiguous	0.197	Stabilizing	0.944	D	0.447	neutral	None	None	None	None	N
Q/K	0.1072	likely_benign	0.1034	benign	0.049	Stabilizing	0.002	N	0.073	neutral	N	0.434150839	None	None	N
Q/L	0.2201	likely_benign	0.2097	benign	0.197	Stabilizing	0.642	D	0.385	neutral	N	0.461953515	None	None	N
Q/M	0.3791	ambiguous	0.3647	ambiguous	0.561	Stabilizing	0.981	D	0.415	neutral	None	None	None	None	N
Q/N	0.312	likely_benign	0.3237	benign	-0.25	Destabilizing	0.495	N	0.347	neutral	None	None	None	None	N
Q/P	0.1098	likely_benign	0.1069	benign	0.07	Stabilizing	0.784	D	0.447	neutral	N	0.347440639	None	None	N
Q/R	0.1556	likely_benign	0.1459	benign	0.217	Stabilizing	0.473	N	0.365	neutral	N	0.436460425	None	None	N
Q/S	0.2489	likely_benign	0.2373	benign	-0.272	Destabilizing	0.495	N	0.37	neutral	None	None	None	None	N
Q/T	0.2361	likely_benign	0.2148	benign	-0.136	Destabilizing	0.704	D	0.327	neutral	None	None	None	None	N
Q/V	0.278	likely_benign	0.2573	benign	0.07	Stabilizing	0.828	D	0.409	neutral	None	None	None	None	N
Q/W	0.7384	likely_pathogenic	0.7297	pathogenic	-0.36	Destabilizing	0.995	D	0.382	neutral	None	None	None	None	N
Q/Y	0.6153	likely_pathogenic	0.5986	pathogenic	-0.118	Destabilizing	0.893	D	0.429	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.