TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25853	77782;77783;77784	chr2:178568575;178568574;178568573	chr2:179433302;179433301;179433300
N2AB	24212	72859;72860;72861	chr2:178568575;178568574;178568573	chr2:179433302;179433301;179433300
N2A	23285	70078;70079;70080	chr2:178568575;178568574;178568573	chr2:179433302;179433301;179433300
N2B	16788	50587;50588;50589	chr2:178568575;178568574;178568573	chr2:179433302;179433301;179433300
Novex-1	16913	50962;50963;50964	chr2:178568575;178568574;178568573	chr2:179433302;179433301;179433300
Novex-2	16980	51163;51164;51165	chr2:178568575;178568574;178568573	chr2:179433302;179433301;179433300
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-136
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.0897
• 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
T/N	None	None	0.998	N	0.745	0.334	0.246773566709	gnomAD-4.0.0	6.84332E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99607E-07	0	0
T/S	None	None	0.979	N	0.615	0.28	0.170165803431	gnomAD-4.0.0	6.84332E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15961E-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
T/A	0.1646	likely_benign	0.1634	benign	-1.258	Destabilizing	0.958	D	0.615	neutral	N	0.485067156	None	None	N
T/C	0.5096	ambiguous	0.5216	ambiguous	-0.985	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
T/D	0.9758	likely_pathogenic	0.9759	pathogenic	-1.991	Destabilizing	0.998	D	0.763	deleterious	None	None	None	None	N
T/E	0.9712	likely_pathogenic	0.9703	pathogenic	-1.701	Destabilizing	0.998	D	0.755	deleterious	None	None	None	None	N
T/F	0.8519	likely_pathogenic	0.8529	pathogenic	-0.977	Destabilizing	0.991	D	0.821	deleterious	None	None	None	None	N
T/G	0.6804	likely_pathogenic	0.6929	pathogenic	-1.715	Destabilizing	0.995	D	0.763	deleterious	None	None	None	None	N
T/H	0.8793	likely_pathogenic	0.8815	pathogenic	-1.795	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
T/I	0.5924	likely_pathogenic	0.5863	pathogenic	-0.02	Destabilizing	0.142	N	0.515	neutral	N	0.460780996	None	None	N
T/K	0.9564	likely_pathogenic	0.9551	pathogenic	-0.203	Destabilizing	0.995	D	0.758	deleterious	None	None	None	None	N
T/L	0.326	likely_benign	0.3281	benign	-0.02	Destabilizing	0.839	D	0.666	neutral	None	None	None	None	N
T/M	0.247	likely_benign	0.2428	benign	-0.258	Destabilizing	0.998	D	0.799	deleterious	None	None	None	None	N
T/N	0.7532	likely_pathogenic	0.7459	pathogenic	-1.269	Destabilizing	0.998	D	0.745	deleterious	N	0.452337979	None	None	N
T/P	0.92	likely_pathogenic	0.9302	pathogenic	-0.404	Destabilizing	0.998	D	0.796	deleterious	N	0.460149112	None	None	N
T/Q	0.8887	likely_pathogenic	0.8836	pathogenic	-0.837	Destabilizing	0.998	D	0.808	deleterious	None	None	None	None	N
T/R	0.9379	likely_pathogenic	0.9358	pathogenic	-0.702	Destabilizing	0.998	D	0.801	deleterious	None	None	None	None	N
T/S	0.2455	likely_benign	0.2367	benign	-1.463	Destabilizing	0.979	D	0.615	neutral	N	0.422863904	None	None	N
T/V	0.3224	likely_benign	0.3253	benign	-0.404	Destabilizing	0.682	D	0.609	neutral	None	None	None	None	N
T/W	0.9774	likely_pathogenic	0.9778	pathogenic	-1.23	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
T/Y	0.9136	likely_pathogenic	0.917	pathogenic	-0.776	Destabilizing	0.995	D	0.824	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.