TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14958	45097;45098;45099	chr2:178622711;178622710;178622709	chr2:179487438;179487437;179487436
N2AB	13317	40174;40175;40176	chr2:178622711;178622710;178622709	chr2:179487438;179487437;179487436
N2A	12390	37393;37394;37395	chr2:178622711;178622710;178622709	chr2:179487438;179487437;179487436
N2B	5893	17902;17903;17904	chr2:178622711;178622710;178622709	chr2:179487438;179487437;179487436
Novex-1	6018	18277;18278;18279	chr2:178622711;178622710;178622709	chr2:179487438;179487437;179487436
Novex-2	6085	18478;18479;18480	chr2:178622711;178622710;178622709	chr2:179487438;179487437;179487436
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-101
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.7422
• 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
M/T	None	None	None	N	0.091	0.072	0.200317383148	gnomAD-4.0.0	1.37397E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.01663E-07	1.17669E-05	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
M/A	0.2549	likely_benign	0.235	benign	-1.051	Destabilizing	0.002	N	0.176	neutral	None	None	None	None	N
M/C	0.8095	likely_pathogenic	0.8488	pathogenic	-0.623	Destabilizing	0.245	N	0.263	neutral	None	None	None	None	N
M/D	0.623	likely_pathogenic	0.6431	pathogenic	-0.037	Destabilizing	0.018	N	0.339	neutral	None	None	None	None	N
M/E	0.3803	ambiguous	0.3543	ambiguous	-0.066	Destabilizing	0.018	N	0.263	neutral	None	None	None	None	N
M/F	0.3867	ambiguous	0.423	ambiguous	-0.44	Destabilizing	0.018	N	0.255	neutral	None	None	None	None	N
M/G	0.5074	ambiguous	0.521	ambiguous	-1.282	Destabilizing	0.008	N	0.279	neutral	None	None	None	None	N
M/H	0.5273	ambiguous	0.5706	pathogenic	-0.353	Destabilizing	0.497	N	0.272	neutral	None	None	None	None	N
M/I	0.2952	likely_benign	0.2828	benign	-0.507	Destabilizing	None	N	0.091	neutral	N	0.420237524	None	None	N
M/K	0.2177	likely_benign	0.2047	benign	-0.016	Destabilizing	0.014	N	0.265	neutral	N	0.385219971	None	None	N
M/L	0.1687	likely_benign	0.1679	benign	-0.507	Destabilizing	None	N	0.083	neutral	N	0.439368017	None	None	N
M/N	0.2791	likely_benign	0.3079	benign	0.201	Stabilizing	0.018	N	0.311	neutral	None	None	None	None	N
M/P	0.4987	ambiguous	0.4381	ambiguous	-0.66	Destabilizing	0.037	N	0.379	neutral	None	None	None	None	N
M/Q	0.2546	likely_benign	0.2622	benign	0.038	Stabilizing	0.085	N	0.257	neutral	None	None	None	None	N
M/R	0.2537	likely_benign	0.2293	benign	0.534	Stabilizing	0.014	N	0.352	neutral	N	0.399451391	None	None	N
M/S	0.2455	likely_benign	0.2555	benign	-0.328	Destabilizing	None	N	0.093	neutral	None	None	None	None	N
M/T	0.1175	likely_benign	0.1042	benign	-0.253	Destabilizing	None	N	0.091	neutral	N	0.349953117	None	None	N
M/V	0.1063	likely_benign	0.0981	benign	-0.66	Destabilizing	None	N	0.093	neutral	N	0.432118821	None	None	N
M/W	0.6978	likely_pathogenic	0.6965	pathogenic	-0.357	Destabilizing	0.497	N	0.266	neutral	None	None	None	None	N
M/Y	0.5804	likely_pathogenic	0.6228	pathogenic	-0.308	Destabilizing	0.085	N	0.358	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.