TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31049	93370;93371;93372	chr2:178548481;178548480;178548479	chr2:179413208;179413207;179413206
N2AB	29408	88447;88448;88449	chr2:178548481;178548480;178548479	chr2:179413208;179413207;179413206
N2A	28481	85666;85667;85668	chr2:178548481;178548480;178548479	chr2:179413208;179413207;179413206
N2B	21984	66175;66176;66177	chr2:178548481;178548480;178548479	chr2:179413208;179413207;179413206
Novex-1	22109	66550;66551;66552	chr2:178548481;178548480;178548479	chr2:179413208;179413207;179413206
Novex-2	22176	66751;66752;66753	chr2:178548481;178548480;178548479	chr2:179413208;179413207;179413206
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-114
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.5344
• 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
H/N	None	None	0.822	N	0.521	0.291	0.239305524855	gnomAD-4.0.0	1.59112E-06	None	None	None	None	I	None	0	0	None	0	2.77269E-05	None	0	0	0	0	0
H/Q	None	None	0.942	N	0.536	0.249	0.271763555656	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
H/Y	None	None	0.966	N	0.527	0.371	0.357313475932	gnomAD-4.0.0	1.59112E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43271E-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
H/A	0.2924	likely_benign	0.2673	benign	0.473	Stabilizing	0.86	D	0.523	neutral	None	None	None	None	I
H/C	0.2097	likely_benign	0.1938	benign	1.155	Stabilizing	0.998	D	0.754	deleterious	None	None	None	None	I
H/D	0.3262	likely_benign	0.2612	benign	-0.108	Destabilizing	0.97	D	0.539	neutral	N	0.375350464	None	None	I
H/E	0.3468	ambiguous	0.2918	benign	-0.06	Destabilizing	0.86	D	0.461	neutral	None	None	None	None	I
H/F	0.3076	likely_benign	0.3016	benign	1.333	Stabilizing	0.993	D	0.621	neutral	None	None	None	None	I
H/G	0.3134	likely_benign	0.2717	benign	0.153	Stabilizing	0.86	D	0.525	neutral	None	None	None	None	I
H/I	0.2903	likely_benign	0.2638	benign	1.312	Stabilizing	0.978	D	0.706	prob.neutral	None	None	None	None	I
H/K	0.2642	likely_benign	0.2293	benign	0.505	Stabilizing	0.754	D	0.506	neutral	None	None	None	None	I
H/L	0.1114	likely_benign	0.0991	benign	1.312	Stabilizing	0.942	D	0.571	neutral	N	0.318209102	None	None	I
H/M	0.4333	ambiguous	0.412	ambiguous	1.019	Stabilizing	0.998	D	0.678	prob.neutral	None	None	None	None	I
H/N	0.0972	likely_benign	0.0874	benign	0.504	Stabilizing	0.822	D	0.521	neutral	N	0.351110954	None	None	I
H/P	0.4908	ambiguous	0.4058	ambiguous	1.058	Stabilizing	0.99	D	0.689	prob.neutral	N	0.437460503	None	None	I
H/Q	0.159	likely_benign	0.1489	benign	0.66	Stabilizing	0.942	D	0.536	neutral	N	0.343048832	None	None	I
H/R	0.1126	likely_benign	0.1063	benign	-0.314	Destabilizing	0.014	N	0.231	neutral	N	0.346723855	None	None	I
H/S	0.1926	likely_benign	0.1661	benign	0.746	Stabilizing	0.86	D	0.531	neutral	None	None	None	None	I
H/T	0.191	likely_benign	0.1716	benign	0.892	Stabilizing	0.956	D	0.547	neutral	None	None	None	None	I
H/V	0.2592	likely_benign	0.2378	benign	1.058	Stabilizing	0.978	D	0.689	prob.neutral	None	None	None	None	I
H/W	0.4819	ambiguous	0.4715	ambiguous	1.326	Stabilizing	0.998	D	0.765	deleterious	None	None	None	None	I
H/Y	0.1134	likely_benign	0.1126	benign	1.564	Stabilizing	0.966	D	0.527	neutral	N	0.426686148	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.