TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15557	46894;46895;46896	chr2:178619648;178619647;178619646	chr2:179484375;179484374;179484373
N2AB	13916	41971;41972;41973	chr2:178619648;178619647;178619646	chr2:179484375;179484374;179484373
N2A	12989	39190;39191;39192	chr2:178619648;178619647;178619646	chr2:179484375;179484374;179484373
N2B	6492	19699;19700;19701	chr2:178619648;178619647;178619646	chr2:179484375;179484374;179484373
Novex-1	6617	20074;20075;20076	chr2:178619648;178619647;178619646	chr2:179484375;179484374;179484373
Novex-2	6684	20275;20276;20277	chr2:178619648;178619647;178619646	chr2:179484375;179484374;179484373
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: Ig-107
• Domain position: 78
• Structural Position: 163
• Q(SASA): 0.4938
• 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/D	None	None	0.001	N	0.223	0.097	0.225902525712	gnomAD-4.0.0	1.59527E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.03306E-05
E/K	None	None	0.549	N	0.581	0.321	0.361958692863	gnomAD-4.0.0	6.84954E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00221E-07	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	0.3063	likely_benign	0.2899	benign	-0.645	Destabilizing	0.201	N	0.556	neutral	N	0.459285523	None	None	N
E/C	0.9473	likely_pathogenic	0.9404	pathogenic	-0.395	Destabilizing	0.992	D	0.666	neutral	None	None	None	None	N
E/D	0.2762	likely_benign	0.2595	benign	-0.699	Destabilizing	0.001	N	0.223	neutral	N	0.443044416	None	None	N
E/F	0.9073	likely_pathogenic	0.896	pathogenic	-0.079	Destabilizing	0.85	D	0.677	prob.neutral	None	None	None	None	N
E/G	0.537	ambiguous	0.483	ambiguous	-0.945	Destabilizing	0.549	D	0.637	neutral	N	0.49943991	None	None	N
E/H	0.8085	likely_pathogenic	0.7663	pathogenic	0.012	Stabilizing	0.972	D	0.608	neutral	None	None	None	None	N
E/I	0.597	likely_pathogenic	0.6028	pathogenic	0.151	Stabilizing	0.217	N	0.651	neutral	None	None	None	None	N
E/K	0.6194	likely_pathogenic	0.5599	ambiguous	-0.116	Destabilizing	0.549	D	0.581	neutral	N	0.394887498	None	None	N
E/L	0.7491	likely_pathogenic	0.7444	pathogenic	0.151	Stabilizing	0.447	N	0.646	neutral	None	None	None	None	N
E/M	0.6873	likely_pathogenic	0.697	pathogenic	0.276	Stabilizing	0.955	D	0.664	neutral	None	None	None	None	N
E/N	0.6212	likely_pathogenic	0.5838	pathogenic	-0.687	Destabilizing	0.617	D	0.589	neutral	None	None	None	None	N
E/P	0.9521	likely_pathogenic	0.9263	pathogenic	-0.094	Destabilizing	0.972	D	0.635	neutral	None	None	None	None	N
E/Q	0.3616	ambiguous	0.3353	benign	-0.586	Destabilizing	0.712	D	0.579	neutral	N	0.488585177	None	None	N
E/R	0.7631	likely_pathogenic	0.71	pathogenic	0.25	Stabilizing	0.92	D	0.616	neutral	None	None	None	None	N
E/S	0.4371	ambiguous	0.3904	ambiguous	-0.884	Destabilizing	0.617	D	0.564	neutral	None	None	None	None	N
E/T	0.4001	ambiguous	0.3719	ambiguous	-0.632	Destabilizing	0.617	D	0.595	neutral	None	None	None	None	N
E/V	0.3355	likely_benign	0.3412	ambiguous	-0.094	Destabilizing	0.004	N	0.47	neutral	N	0.47350241	None	None	N
E/W	0.9647	likely_pathogenic	0.9587	pathogenic	0.211	Stabilizing	0.992	D	0.661	neutral	None	None	None	None	N
E/Y	0.841	likely_pathogenic	0.8361	pathogenic	0.191	Stabilizing	0.92	D	0.684	prob.neutral	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.