TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22325	67198;67199;67200	chr2:178580406;178580405;178580404	chr2:179445133;179445132;179445131
N2AB	20684	62275;62276;62277	chr2:178580406;178580405;178580404	chr2:179445133;179445132;179445131
N2A	19757	59494;59495;59496	chr2:178580406;178580405;178580404	chr2:179445133;179445132;179445131
N2B	13260	40003;40004;40005	chr2:178580406;178580405;178580404	chr2:179445133;179445132;179445131
Novex-1	13385	40378;40379;40380	chr2:178580406;178580405;178580404	chr2:179445133;179445132;179445131
Novex-2	13452	40579;40580;40581	chr2:178580406;178580405;178580404	chr2:179445133;179445132;179445131
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-126
• Domain position: 61
• Structural Position: 145
• Q(SASA): 0.2928
• 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
N/S	None	None	0.919	N	0.432	0.303	0.247322355667	gnomAD-4.0.0	1.5924E-06	None	None	None	None	I	None	0	0	None	0	2.77886E-05	None	0	0	0	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
N/A	0.7113	likely_pathogenic	0.7365	pathogenic	-0.83	Destabilizing	0.938	D	0.563	neutral	None	None	None	None	I
N/C	0.539	ambiguous	0.5874	pathogenic	0.172	Stabilizing	1.0	D	0.79	deleterious	None	None	None	None	I
N/D	0.1903	likely_benign	0.2301	benign	-0.308	Destabilizing	0.958	D	0.49	neutral	N	0.505102152	None	None	I
N/E	0.8156	likely_pathogenic	0.8464	pathogenic	-0.24	Destabilizing	0.968	D	0.569	neutral	None	None	None	None	I
N/F	0.9098	likely_pathogenic	0.9168	pathogenic	-0.701	Destabilizing	0.995	D	0.792	deleterious	None	None	None	None	I
N/G	0.5016	ambiguous	0.5472	ambiguous	-1.147	Destabilizing	0.968	D	0.447	neutral	None	None	None	None	I
N/H	0.3136	likely_benign	0.3212	benign	-0.989	Destabilizing	0.998	D	0.7	prob.neutral	N	0.504699507	None	None	I
N/I	0.8074	likely_pathogenic	0.819	pathogenic	-0.036	Destabilizing	0.988	D	0.781	deleterious	N	0.486479705	None	None	I
N/K	0.8042	likely_pathogenic	0.834	pathogenic	-0.287	Destabilizing	0.958	D	0.589	neutral	N	0.485937601	None	None	I
N/L	0.6501	likely_pathogenic	0.6615	pathogenic	-0.036	Destabilizing	0.982	D	0.693	prob.neutral	None	None	None	None	I
N/M	0.7403	likely_pathogenic	0.7517	pathogenic	0.473	Stabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
N/P	0.9666	likely_pathogenic	0.9739	pathogenic	-0.271	Destabilizing	0.995	D	0.741	deleterious	None	None	None	None	I
N/Q	0.7562	likely_pathogenic	0.7742	pathogenic	-0.78	Destabilizing	0.995	D	0.677	prob.neutral	None	None	None	None	I
N/R	0.8248	likely_pathogenic	0.8433	pathogenic	-0.333	Destabilizing	0.991	D	0.682	prob.neutral	None	None	None	None	I
N/S	0.134	likely_benign	0.1395	benign	-0.781	Destabilizing	0.919	D	0.432	neutral	N	0.457521636	None	None	I
N/T	0.1871	likely_benign	0.206	benign	-0.526	Destabilizing	0.067	N	0.345	neutral	N	0.475934038	None	None	I
N/V	0.7443	likely_pathogenic	0.7643	pathogenic	-0.271	Destabilizing	0.982	D	0.706	prob.neutral	None	None	None	None	I
N/W	0.9675	likely_pathogenic	0.9704	pathogenic	-0.514	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
N/Y	0.5942	likely_pathogenic	0.628	pathogenic	-0.323	Destabilizing	0.998	D	0.762	deleterious	N	0.498000595	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.