TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2213	6862;6863;6864	chr2:178775074;178775073;178775072	chr2:179639801;179639800;179639799
N2AB	2213	6862;6863;6864	chr2:178775074;178775073;178775072	chr2:179639801;179639800;179639799
N2A	2213	6862;6863;6864	chr2:178775074;178775073;178775072	chr2:179639801;179639800;179639799
N2B	2167	6724;6725;6726	chr2:178775074;178775073;178775072	chr2:179639801;179639800;179639799
Novex-1	2167	6724;6725;6726	chr2:178775074;178775073;178775072	chr2:179639801;179639800;179639799
Novex-2	2167	6724;6725;6726	chr2:178775074;178775073;178775072	chr2:179639801;179639800;179639799
Novex-3	2213	6862;6863;6864	chr2:178775074;178775073;178775072	chr2:179639801;179639800;179639799

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-11
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.4778
• 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
E/D	rs745719077	-0.562	0.999	D	0.501	0.236	0.268660756437	gnomAD-2.1.1	1.42E-05	None	None	None	None	N	None	4.01E-05	0	None	0	0	None	0	None	0	2.33E-05	0
E/D	rs745719077	-0.562	0.999	D	0.501	0.236	0.268660756437	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	2.94E-05	0	0
E/D	rs745719077	-0.562	0.999	D	0.501	0.236	0.268660756437	gnomAD-4.0.0	1.85881E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.69494E-06	0	1.60041E-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
E/A	0.0932	likely_benign	0.1057	benign	-0.856	Destabilizing	0.767	D	0.326	neutral	D	0.559635818	None	None	N
E/C	0.7722	likely_pathogenic	0.7923	pathogenic	-0.649	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
E/D	0.1973	likely_benign	0.2127	benign	-0.903	Destabilizing	0.999	D	0.501	neutral	D	0.562285506	None	None	N
E/F	0.6046	likely_pathogenic	0.6222	pathogenic	-0.223	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
E/G	0.2072	likely_benign	0.2515	benign	-1.179	Destabilizing	0.996	D	0.573	neutral	D	0.709832988	None	None	N
E/H	0.4629	ambiguous	0.4957	ambiguous	-0.237	Destabilizing	1.0	D	0.611	neutral	None	None	None	None	N
E/I	0.1748	likely_benign	0.1997	benign	0.02	Stabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
E/K	0.1427	likely_benign	0.1672	benign	-0.79	Destabilizing	0.998	D	0.557	neutral	N	0.499164703	None	None	N
E/L	0.1923	likely_benign	0.2124	benign	0.02	Stabilizing	0.999	D	0.635	neutral	None	None	None	None	N
E/M	0.2664	likely_benign	0.2965	benign	0.242	Stabilizing	1.0	D	0.646	neutral	None	None	None	None	N
E/N	0.2735	likely_benign	0.3033	benign	-1.169	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	N
E/P	0.2659	likely_benign	0.2999	benign	-0.253	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
E/Q	0.1298	likely_benign	0.1488	benign	-1.045	Destabilizing	1.0	D	0.57	neutral	D	0.568835767	None	None	N
E/R	0.2434	likely_benign	0.2709	benign	-0.324	Destabilizing	1.0	D	0.635	neutral	None	None	None	None	N
E/S	0.2038	likely_benign	0.2311	benign	-1.453	Destabilizing	0.994	D	0.562	neutral	None	None	None	None	N
E/T	0.1762	likely_benign	0.2073	benign	-1.194	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	N
E/V	0.105	likely_benign	0.1219	benign	-0.253	Destabilizing	0.999	D	0.569	neutral	D	0.533397478	None	None	N
E/W	0.8755	likely_pathogenic	0.8962	pathogenic	0.041	Stabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
E/Y	0.5854	likely_pathogenic	0.6116	pathogenic	-0.001	Destabilizing	1.0	D	0.667	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.