TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33449	100570;100571;100572	chr2:178536402;178536401;178536400	chr2:179401129;179401128;179401127
N2AB	31808	95647;95648;95649	chr2:178536402;178536401;178536400	chr2:179401129;179401128;179401127
N2A	30881	92866;92867;92868	chr2:178536402;178536401;178536400	chr2:179401129;179401128;179401127
N2B	24384	73375;73376;73377	chr2:178536402;178536401;178536400	chr2:179401129;179401128;179401127
Novex-1	24509	73750;73751;73752	chr2:178536402;178536401;178536400	chr2:179401129;179401128;179401127
Novex-2	24576	73951;73952;73953	chr2:178536402;178536401;178536400	chr2:179401129;179401128;179401127
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-131
• Domain position: 58
• Structural Position: 88
• Q(SASA): 0.3092
• 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/A	rs1218969890	-1.049	0.992	N	0.571	0.482	0.422524665647	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
E/A	rs1218969890	-1.049	0.992	N	0.571	0.482	0.422524665647	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/A	rs1218969890	-1.049	0.992	N	0.571	0.482	0.422524665647	gnomAD-4.0.0	3.71835E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.23816E-06	0	1.60118E-05
E/Q	None	None	0.916	N	0.363	0.105	0.229264304666	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
E/A	0.373	ambiguous	0.4205	ambiguous	-0.11	Destabilizing	0.992	D	0.571	neutral	N	0.487948038	None	None	N
E/C	0.9554	likely_pathogenic	0.9672	pathogenic	-0.383	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/D	0.1869	likely_benign	0.1764	benign	-0.489	Destabilizing	0.992	D	0.481	neutral	N	0.439215515	None	None	N
E/F	0.9508	likely_pathogenic	0.9647	pathogenic	0.363	Stabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
E/G	0.2673	likely_benign	0.3341	benign	-0.352	Destabilizing	0.999	D	0.7	prob.neutral	N	0.483198366	None	None	N
E/H	0.8121	likely_pathogenic	0.8416	pathogenic	0.855	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
E/I	0.8667	likely_pathogenic	0.8988	pathogenic	0.51	Stabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/K	0.4426	ambiguous	0.5422	ambiguous	0.336	Stabilizing	0.984	D	0.505	neutral	N	0.50328285	None	None	N
E/L	0.8361	likely_pathogenic	0.8601	pathogenic	0.51	Stabilizing	0.998	D	0.765	deleterious	None	None	None	None	N
E/M	0.8375	likely_pathogenic	0.862	pathogenic	0.236	Stabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
E/N	0.4104	ambiguous	0.4483	ambiguous	-0.35	Destabilizing	0.999	D	0.682	prob.neutral	None	None	None	None	N
E/P	0.9316	likely_pathogenic	0.955	pathogenic	0.324	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
E/Q	0.3129	likely_benign	0.3315	benign	-0.233	Destabilizing	0.916	D	0.363	neutral	N	0.470767787	None	None	N
E/R	0.6407	likely_pathogenic	0.722	pathogenic	0.753	Stabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	N
E/S	0.3825	ambiguous	0.4329	ambiguous	-0.472	Destabilizing	0.994	D	0.573	neutral	None	None	None	None	N
E/T	0.5004	ambiguous	0.5664	pathogenic	-0.247	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
E/V	0.6716	likely_pathogenic	0.7248	pathogenic	0.324	Stabilizing	0.999	D	0.736	prob.delet.	N	0.519676454	None	None	N
E/W	0.9845	likely_pathogenic	0.9892	pathogenic	0.558	Stabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/Y	0.8972	likely_pathogenic	0.9233	pathogenic	0.631	Stabilizing	1.0	D	0.799	deleterious	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.