TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27392	82399;82400;82401	chr2:178563958;178563957;178563956	chr2:179428685;179428684;179428683
N2AB	25751	77476;77477;77478	chr2:178563958;178563957;178563956	chr2:179428685;179428684;179428683
N2A	24824	74695;74696;74697	chr2:178563958;178563957;178563956	chr2:179428685;179428684;179428683
N2B	18327	55204;55205;55206	chr2:178563958;178563957;178563956	chr2:179428685;179428684;179428683
Novex-1	18452	55579;55580;55581	chr2:178563958;178563957;178563956	chr2:179428685;179428684;179428683
Novex-2	18519	55780;55781;55782	chr2:178563958;178563957;178563956	chr2:179428685;179428684;179428683
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-87
• Domain position: 24
• Structural Position: 25
• Q(SASA): 0.4261
• 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
N/I	None	None	0.627	N	0.641	0.157	0.430808444494	gnomAD-4.0.0	1.5914E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85863E-06	0	0
N/K	rs1421975284	-0.023	0.193	N	0.384	0.131	0.132336055621	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	6.43501E-04	None	0	None	0	0	0
N/K	rs1421975284	-0.023	0.193	N	0.384	0.131	0.132336055621	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.93424E-04	None	0	0	0	0	0
N/K	rs1421975284	-0.023	0.193	N	0.384	0.131	0.132336055621	gnomAD-4.0.0	6.57505E-06	None	None	None	None	N	None	0	0	None	0	1.93424E-04	None	0	0	0	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
N/A	0.1173	likely_benign	0.1369	benign	-0.745	Destabilizing	0.002	N	0.377	neutral	None	None	None	None	N
N/C	0.1612	likely_benign	0.1774	benign	0.065	Stabilizing	0.944	D	0.616	neutral	None	None	None	None	N
N/D	0.137	likely_benign	0.1555	benign	-0.353	Destabilizing	0.324	N	0.396	neutral	N	0.454448753	None	None	N
N/E	0.1877	likely_benign	0.2157	benign	-0.27	Destabilizing	0.241	N	0.395	neutral	None	None	None	None	N
N/F	0.2725	likely_benign	0.3274	benign	-0.575	Destabilizing	0.818	D	0.628	neutral	None	None	None	None	N
N/G	0.1502	likely_benign	0.176	benign	-1.068	Destabilizing	0.002	N	0.186	neutral	None	None	None	None	N
N/H	0.0784	likely_benign	0.0921	benign	-0.857	Destabilizing	0.003	N	0.271	neutral	D	0.522540614	None	None	N
N/I	0.1193	likely_benign	0.1356	benign	0.068	Stabilizing	0.627	D	0.641	neutral	N	0.489236117	None	None	N
N/K	0.1175	likely_benign	0.1478	benign	-0.286	Destabilizing	0.193	N	0.384	neutral	N	0.396843244	None	None	N
N/L	0.1007	likely_benign	0.1174	benign	0.068	Stabilizing	0.388	N	0.597	neutral	None	None	None	None	N
N/M	0.1612	likely_benign	0.1835	benign	0.355	Stabilizing	0.981	D	0.617	neutral	None	None	None	None	N
N/P	0.7086	likely_pathogenic	0.7488	pathogenic	-0.173	Destabilizing	0.818	D	0.644	neutral	None	None	None	None	N
N/Q	0.146	likely_benign	0.1756	benign	-0.748	Destabilizing	0.69	D	0.514	neutral	None	None	None	None	N
N/R	0.1623	likely_benign	0.2026	benign	-0.339	Destabilizing	0.69	D	0.493	neutral	None	None	None	None	N
N/S	0.0741	likely_benign	0.0836	benign	-0.782	Destabilizing	0.001	N	0.174	neutral	N	0.394533658	None	None	N
N/T	0.0929	likely_benign	0.1062	benign	-0.512	Destabilizing	0.193	N	0.391	neutral	N	0.438420508	None	None	N
N/V	0.1335	likely_benign	0.152	benign	-0.173	Destabilizing	0.527	D	0.619	neutral	None	None	None	None	N
N/W	0.5473	ambiguous	0.5989	pathogenic	-0.41	Destabilizing	0.981	D	0.661	neutral	None	None	None	None	N
N/Y	0.0969	likely_benign	0.1055	benign	-0.196	Destabilizing	0.457	N	0.649	neutral	N	0.499010394	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.