TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20528	61807;61808;61809	chr2:178590143;178590142;178590141	chr2:179454870;179454869;179454868
N2AB	18887	56884;56885;56886	chr2:178590143;178590142;178590141	chr2:179454870;179454869;179454868
N2A	17960	54103;54104;54105	chr2:178590143;178590142;178590141	chr2:179454870;179454869;179454868
N2B	11463	34612;34613;34614	chr2:178590143;178590142;178590141	chr2:179454870;179454869;179454868
Novex-1	11588	34987;34988;34989	chr2:178590143;178590142;178590141	chr2:179454870;179454869;179454868
Novex-2	11655	35188;35189;35190	chr2:178590143;178590142;178590141	chr2:179454870;179454869;179454868
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-121
• Domain position: 50
• Structural Position: 130
• Q(SASA): 0.512
• 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
D/E	rs374601610	-0.161	None	N	0.177	0.116	0.0884992946249	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
D/E	rs374601610	-0.161	None	N	0.177	0.116	0.0884992946249	gnomAD-4.0.0	6.84431E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99672E-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
D/A	0.1619	likely_benign	0.1907	benign	-0.114	Destabilizing	0.062	N	0.325	neutral	N	0.473741882	None	None	N
D/C	0.5086	ambiguous	0.598	pathogenic	-0.161	Destabilizing	0.935	D	0.455	neutral	None	None	None	None	N
D/E	0.1189	likely_benign	0.1274	benign	-0.241	Destabilizing	None	N	0.177	neutral	N	0.44840072	None	None	N
D/F	0.4823	ambiguous	0.5697	pathogenic	-0.003	Destabilizing	0.791	D	0.404	neutral	None	None	None	None	N
D/G	0.158	likely_benign	0.2035	benign	-0.303	Destabilizing	0.117	N	0.264	neutral	N	0.449019582	None	None	N
D/H	0.2329	likely_benign	0.2803	benign	0.335	Stabilizing	0.484	N	0.275	neutral	N	0.485556386	None	None	N
D/I	0.2692	likely_benign	0.3229	benign	0.333	Stabilizing	0.555	D	0.403	neutral	None	None	None	None	N
D/K	0.3076	likely_benign	0.378	ambiguous	0.24	Stabilizing	0.081	N	0.253	neutral	None	None	None	None	N
D/L	0.3102	likely_benign	0.3772	ambiguous	0.333	Stabilizing	0.38	N	0.391	neutral	None	None	None	None	N
D/M	0.5082	ambiguous	0.5673	pathogenic	0.215	Stabilizing	0.935	D	0.417	neutral	None	None	None	None	N
D/N	0.1022	likely_benign	0.113	benign	-0.07	Destabilizing	0.001	N	0.153	neutral	N	0.415309654	None	None	N
D/P	0.6406	likely_pathogenic	0.6927	pathogenic	0.206	Stabilizing	0.555	D	0.285	neutral	None	None	None	None	N
D/Q	0.2614	likely_benign	0.3053	benign	-0.019	Destabilizing	0.235	N	0.256	neutral	None	None	None	None	N
D/R	0.3508	ambiguous	0.4469	ambiguous	0.506	Stabilizing	0.235	N	0.357	neutral	None	None	None	None	N
D/S	0.1276	likely_benign	0.1475	benign	-0.18	Destabilizing	0.035	N	0.275	neutral	None	None	None	None	N
D/T	0.2057	likely_benign	0.2303	benign	-0.031	Destabilizing	0.149	N	0.248	neutral	None	None	None	None	N
D/V	0.156	likely_benign	0.19	benign	0.206	Stabilizing	0.317	N	0.391	neutral	N	0.488999336	None	None	N
D/W	0.7966	likely_pathogenic	0.8548	pathogenic	0.099	Stabilizing	0.935	D	0.534	neutral	None	None	None	None	N
D/Y	0.1877	likely_benign	0.246	benign	0.223	Stabilizing	0.741	D	0.406	neutral	N	0.518052806	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.