TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26386	79381;79382;79383	chr2:178566976;178566975;178566974	chr2:179431703;179431702;179431701
N2AB	24745	74458;74459;74460	chr2:178566976;178566975;178566974	chr2:179431703;179431702;179431701
N2A	23818	71677;71678;71679	chr2:178566976;178566975;178566974	chr2:179431703;179431702;179431701
N2B	17321	52186;52187;52188	chr2:178566976;178566975;178566974	chr2:179431703;179431702;179431701
Novex-1	17446	52561;52562;52563	chr2:178566976;178566975;178566974	chr2:179431703;179431702;179431701
Novex-2	17513	52762;52763;52764	chr2:178566976;178566975;178566974	chr2:179431703;179431702;179431701
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-80
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.7033
• 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
L/F	rs1706115983	None	0.087	N	0.255	0.068	0.257292322809	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

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
L/A	0.1224	likely_benign	0.1302	benign	-0.655	Destabilizing	None	N	0.097	neutral	None	None	None	None	I
L/C	0.2842	likely_benign	0.2933	benign	-0.621	Destabilizing	0.439	N	0.479	neutral	None	None	None	None	I
L/D	0.6243	likely_pathogenic	0.6343	pathogenic	-0.06	Destabilizing	0.035	N	0.531	neutral	None	None	None	None	I
L/E	0.2925	likely_benign	0.3018	benign	-0.16	Destabilizing	0.035	N	0.566	neutral	None	None	None	None	I
L/F	0.171	likely_benign	0.1691	benign	-0.711	Destabilizing	0.087	N	0.255	neutral	N	0.484211513	None	None	I
L/G	0.3724	ambiguous	0.3769	ambiguous	-0.809	Destabilizing	0.007	N	0.583	neutral	None	None	None	None	I
L/H	0.1707	likely_benign	0.175	benign	-0.09	Destabilizing	0.371	N	0.431	neutral	N	0.479883128	None	None	I
L/I	0.0842	likely_benign	0.0825	benign	-0.38	Destabilizing	0.006	N	0.261	neutral	N	0.430627744	None	None	I
L/K	0.1456	likely_benign	0.166	benign	-0.232	Destabilizing	0.035	N	0.553	neutral	None	None	None	None	I
L/M	0.1049	likely_benign	0.1086	benign	-0.333	Destabilizing	0.204	N	0.332	neutral	None	None	None	None	I
L/N	0.2797	likely_benign	0.2943	benign	-0.033	Destabilizing	0.112	N	0.519	neutral	None	None	None	None	I
L/P	0.0704	likely_benign	0.0732	benign	-0.438	Destabilizing	None	N	0.128	neutral	N	0.336370788	None	None	I
L/Q	0.0997	likely_benign	0.1079	benign	-0.293	Destabilizing	0.204	N	0.523	neutral	None	None	None	None	I
L/R	0.109	likely_benign	0.1218	benign	0.329	Stabilizing	0.087	N	0.509	neutral	N	0.450733657	None	None	I
L/S	0.1688	likely_benign	0.1787	benign	-0.523	Destabilizing	0.007	N	0.463	neutral	None	None	None	None	I
L/T	0.1109	likely_benign	0.1192	benign	-0.515	Destabilizing	None	N	0.141	neutral	None	None	None	None	I
L/V	0.0662	likely_benign	0.0652	benign	-0.438	Destabilizing	None	N	0.076	neutral	N	0.364015963	None	None	I
L/W	0.3266	likely_benign	0.3146	benign	-0.689	Destabilizing	0.747	D	0.503	neutral	None	None	None	None	I
L/Y	0.3278	likely_benign	0.3261	benign	-0.428	Destabilizing	0.204	N	0.468	neutral	None	None	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.