TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18854	56785;56786;56787	chr2:178599233;178599232;178599231	chr2:179463960;179463959;179463958
N2AB	17213	51862;51863;51864	chr2:178599233;178599232;178599231	chr2:179463960;179463959;179463958
N2A	16286	49081;49082;49083	chr2:178599233;178599232;178599231	chr2:179463960;179463959;179463958
N2B	9789	29590;29591;29592	chr2:178599233;178599232;178599231	chr2:179463960;179463959;179463958
Novex-1	9914	29965;29966;29967	chr2:178599233;178599232;178599231	chr2:179463960;179463959;179463958
Novex-2	9981	30166;30167;30168	chr2:178599233;178599232;178599231	chr2:179463960;179463959;179463958
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: Fn3-24
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.3855
• 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/V	None	None	0.994	N	0.799	0.443	0.486779940545	gnomAD-4.0.0	1.43365E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.39454E-05	1.73762E-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	0.2388	likely_benign	0.2089	benign	-0.942	Destabilizing	0.958	D	0.667	neutral	N	0.477511304	None	None	N
E/C	0.8532	likely_pathogenic	0.8309	pathogenic	-0.532	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
E/D	0.2513	likely_benign	0.2088	benign	-1.13	Destabilizing	0.067	N	0.207	neutral	N	0.472560553	None	None	N
E/F	0.8866	likely_pathogenic	0.8763	pathogenic	-0.427	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/G	0.3539	ambiguous	0.3134	benign	-1.316	Destabilizing	0.988	D	0.754	deleterious	N	0.48172804	None	None	N
E/H	0.5554	ambiguous	0.5267	ambiguous	-0.786	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
E/I	0.4606	ambiguous	0.4538	ambiguous	0.081	Stabilizing	0.995	D	0.807	deleterious	None	None	None	None	N
E/K	0.1922	likely_benign	0.1834	benign	-0.85	Destabilizing	0.958	D	0.553	neutral	N	0.51222762	None	None	N
E/L	0.542	ambiguous	0.5129	ambiguous	0.081	Stabilizing	0.995	D	0.803	deleterious	None	None	None	None	N
E/M	0.5612	ambiguous	0.5568	ambiguous	0.574	Stabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
E/N	0.3845	ambiguous	0.3333	benign	-1.231	Destabilizing	0.982	D	0.712	prob.delet.	None	None	None	None	N
E/P	0.671	likely_pathogenic	0.5788	pathogenic	-0.239	Destabilizing	0.995	D	0.811	deleterious	None	None	None	None	N
E/Q	0.1308	likely_benign	0.1286	benign	-1.083	Destabilizing	0.994	D	0.654	neutral	N	0.497028881	None	None	N
E/R	0.2994	likely_benign	0.2817	benign	-0.588	Destabilizing	0.995	D	0.722	prob.delet.	None	None	None	None	N
E/S	0.2707	likely_benign	0.2312	benign	-1.584	Destabilizing	0.968	D	0.597	neutral	None	None	None	None	N
E/T	0.2585	likely_benign	0.2422	benign	-1.279	Destabilizing	0.991	D	0.773	deleterious	None	None	None	None	N
E/V	0.2913	likely_benign	0.277	benign	-0.239	Destabilizing	0.994	D	0.799	deleterious	N	0.469308551	None	None	N
E/W	0.9532	likely_pathogenic	0.9525	pathogenic	-0.212	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/Y	0.7938	likely_pathogenic	0.7775	pathogenic	-0.2	Destabilizing	1.0	D	0.786	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.