TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16007	48244;48245;48246	chr2:178616870;178616869;178616868	chr2:179481597;179481596;179481595
N2AB	14366	43321;43322;43323	chr2:178616870;178616869;178616868	chr2:179481597;179481596;179481595
N2A	13439	40540;40541;40542	chr2:178616870;178616869;178616868	chr2:179481597;179481596;179481595
N2B	6942	21049;21050;21051	chr2:178616870;178616869;178616868	chr2:179481597;179481596;179481595
Novex-1	7067	21424;21425;21426	chr2:178616870;178616869;178616868	chr2:179481597;179481596;179481595
Novex-2	7134	21625;21626;21627	chr2:178616870;178616869;178616868	chr2:179481597;179481596;179481595
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-109
• Domain position: 40
• Structural Position: 102
• Q(SASA): 0.9654
• 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/A	None	None	0.309	N	0.301	0.193	0.236890367714	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
D/G	None	None	0.007	N	0.231	0.156	0.154104182512	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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	0.1585	likely_benign	0.1699	benign	0.083	Stabilizing	0.309	N	0.301	neutral	N	0.436280322	None	None	N
D/C	0.5144	ambiguous	0.5423	ambiguous	-0.192	Destabilizing	0.996	D	0.356	neutral	None	None	None	None	N
D/E	0.1164	likely_benign	0.1242	benign	-0.436	Destabilizing	0.003	N	0.149	neutral	N	0.434530289	None	None	N
D/F	0.557	ambiguous	0.5607	ambiguous	-0.074	Destabilizing	0.02	N	0.351	neutral	None	None	None	None	N
D/G	0.1343	likely_benign	0.1421	benign	0.003	Stabilizing	0.007	N	0.231	neutral	N	0.436987728	None	None	N
D/H	0.2338	likely_benign	0.2515	benign	0.57	Stabilizing	0.939	D	0.289	neutral	N	0.452808236	None	None	N
D/I	0.3468	ambiguous	0.3626	ambiguous	0.223	Stabilizing	0.835	D	0.34	neutral	None	None	None	None	N
D/K	0.2093	likely_benign	0.2372	benign	0.394	Stabilizing	0.59	D	0.277	neutral	None	None	None	None	N
D/L	0.3051	likely_benign	0.3304	benign	0.223	Stabilizing	0.59	D	0.346	neutral	None	None	None	None	N
D/M	0.5562	ambiguous	0.5794	pathogenic	-0.009	Destabilizing	0.987	D	0.327	neutral	None	None	None	None	N
D/N	0.0988	likely_benign	0.1015	benign	0.192	Stabilizing	0.684	D	0.319	neutral	N	0.453580143	None	None	N
D/P	0.338	likely_benign	0.3599	ambiguous	0.194	Stabilizing	0.953	D	0.311	neutral	None	None	None	None	N
D/Q	0.2418	likely_benign	0.2621	benign	0.177	Stabilizing	0.835	D	0.274	neutral	None	None	None	None	N
D/R	0.2874	likely_benign	0.3062	benign	0.591	Stabilizing	0.91	D	0.335	neutral	None	None	None	None	N
D/S	0.1039	likely_benign	0.1116	benign	0.107	Stabilizing	0.742	D	0.247	neutral	None	None	None	None	N
D/T	0.2147	likely_benign	0.2338	benign	0.179	Stabilizing	0.742	D	0.33	neutral	None	None	None	None	N
D/V	0.2082	likely_benign	0.2198	benign	0.194	Stabilizing	0.684	D	0.36	neutral	N	0.521800076	None	None	N
D/W	0.7889	likely_pathogenic	0.7959	pathogenic	-0.073	Destabilizing	0.996	D	0.359	neutral	None	None	None	None	N
D/Y	0.2337	likely_benign	0.2367	benign	0.138	Stabilizing	0.792	D	0.343	neutral	N	0.52073822	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.