TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20524	61795;61796;61797	chr2:178590155;178590154;178590153	chr2:179454882;179454881;179454880
N2AB	18883	56872;56873;56874	chr2:178590155;178590154;178590153	chr2:179454882;179454881;179454880
N2A	17956	54091;54092;54093	chr2:178590155;178590154;178590153	chr2:179454882;179454881;179454880
N2B	11459	34600;34601;34602	chr2:178590155;178590154;178590153	chr2:179454882;179454881;179454880
Novex-1	11584	34975;34976;34977	chr2:178590155;178590154;178590153	chr2:179454882;179454881;179454880
Novex-2	11651	35176;35177;35178	chr2:178590155;178590154;178590153	chr2:179454882;179454881;179454880
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-121
• Domain position: 46
• Structural Position: 122
• Q(SASA): 0.3569
• 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/G	None	None	0.012	N	0.355	0.223	0.258779203287	gnomAD-4.0.0	1.5926E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86035E-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	0.1439	likely_benign	0.1798	benign	-0.509	Destabilizing	0.024	N	0.358	neutral	N	0.460676584	None	None	N
D/C	0.4549	ambiguous	0.5683	pathogenic	-0.363	Destabilizing	0.864	D	0.429	neutral	None	None	None	None	N
D/E	0.1034	likely_benign	0.1233	benign	-0.924	Destabilizing	None	N	0.1	neutral	N	0.414096145	None	None	N
D/F	0.4402	ambiguous	0.545	ambiguous	-0.266	Destabilizing	0.214	N	0.46	neutral	None	None	None	None	N
D/G	0.1875	likely_benign	0.2629	benign	-0.883	Destabilizing	0.012	N	0.355	neutral	N	0.470874935	None	None	N
D/H	0.1947	likely_benign	0.2546	benign	-0.737	Destabilizing	0.171	N	0.385	neutral	N	0.441245461	None	None	N
D/I	0.2232	likely_benign	0.2981	benign	0.485	Stabilizing	0.038	N	0.445	neutral	None	None	None	None	N
D/K	0.3123	likely_benign	0.4263	ambiguous	-0.677	Destabilizing	0.016	N	0.345	neutral	None	None	None	None	N
D/L	0.264	likely_benign	0.3351	benign	0.485	Stabilizing	0.016	N	0.383	neutral	None	None	None	None	N
D/M	0.4053	ambiguous	0.4967	ambiguous	0.924	Stabilizing	0.007	N	0.363	neutral	None	None	None	None	N
D/N	0.0824	likely_benign	0.1043	benign	-1.013	Destabilizing	None	N	0.148	neutral	N	0.453249179	None	None	N
D/P	0.8333	likely_pathogenic	0.9258	pathogenic	0.179	Stabilizing	0.136	N	0.371	neutral	None	None	None	None	N
D/Q	0.2241	likely_benign	0.2936	benign	-0.849	Destabilizing	0.003	N	0.171	neutral	None	None	None	None	N
D/R	0.3423	ambiguous	0.4677	ambiguous	-0.62	Destabilizing	0.072	N	0.385	neutral	None	None	None	None	N
D/S	0.1046	likely_benign	0.1214	benign	-1.349	Destabilizing	0.016	N	0.272	neutral	None	None	None	None	N
D/T	0.1507	likely_benign	0.1903	benign	-1.038	Destabilizing	None	N	0.163	neutral	None	None	None	None	N
D/V	0.1487	likely_benign	0.1919	benign	0.179	Stabilizing	0.012	N	0.382	neutral	N	0.406612813	None	None	N
D/W	0.8009	likely_pathogenic	0.8666	pathogenic	-0.222	Destabilizing	0.864	D	0.445	neutral	None	None	None	None	N
D/Y	0.1956	likely_benign	0.2619	benign	-0.057	Destabilizing	0.56	D	0.463	neutral	N	0.484958953	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.