TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9962	30109;30110;30111	chr2:178704588;178704587;178704586	chr2:179569315;179569314;179569313
N2AB	9645	29158;29159;29160	chr2:178704588;178704587;178704586	chr2:179569315;179569314;179569313
N2A	8718	26377;26378;26379	chr2:178704588;178704587;178704586	chr2:179569315;179569314;179569313
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-84
• Domain position: 63
• Structural Position: 143
• Q(SASA): 0.2839
• 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/S	None	None	0.002	None	0.1	0.128	0.162503812791	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
N/A	0.5593	ambiguous	0.6643	pathogenic	-0.264	Destabilizing	0.016	N	0.333	neutral	None	None	None	None	N
N/C	0.75	likely_pathogenic	0.8014	pathogenic	0.439	Stabilizing	0.864	D	0.419	neutral	None	None	None	None	N
N/D	0.1646	likely_benign	0.1862	benign	-0.918	Destabilizing	None	N	0.073	neutral	None	None	None	None	N
N/E	0.5643	likely_pathogenic	0.6652	pathogenic	-0.909	Destabilizing	0.016	N	0.257	neutral	None	None	None	None	N
N/F	0.8424	likely_pathogenic	0.8844	pathogenic	-0.5	Destabilizing	0.12	N	0.49	neutral	None	None	None	None	N
N/G	0.4964	ambiguous	0.5781	pathogenic	-0.505	Destabilizing	0.031	N	0.246	neutral	None	None	None	None	N
N/H	0.2045	likely_benign	0.2214	benign	-0.613	Destabilizing	0.171	N	0.301	neutral	None	None	None	None	N
N/I	0.7969	likely_pathogenic	0.8767	pathogenic	0.301	Stabilizing	0.171	N	0.495	neutral	None	None	None	None	N
N/K	0.4217	ambiguous	0.5176	ambiguous	-0.043	Destabilizing	0.001	N	0.102	neutral	None	None	None	None	N
N/L	0.7347	likely_pathogenic	0.815	pathogenic	0.301	Stabilizing	0.072	N	0.427	neutral	None	None	None	None	N
N/M	0.7484	likely_pathogenic	0.8252	pathogenic	0.965	Stabilizing	0.628	D	0.409	neutral	None	None	None	None	N
N/P	0.979	likely_pathogenic	0.9863	pathogenic	0.142	Stabilizing	0.356	N	0.477	neutral	None	None	None	None	N
N/Q	0.5034	ambiguous	0.574	pathogenic	-0.751	Destabilizing	0.072	N	0.267	neutral	None	None	None	None	N
N/R	0.5047	ambiguous	0.5948	pathogenic	0.088	Stabilizing	None	N	0.215	neutral	None	None	None	None	N
N/S	0.2175	likely_benign	0.2619	benign	-0.372	Destabilizing	0.002	N	0.1	neutral	None	None	None	None	N
N/T	0.4807	ambiguous	0.5848	pathogenic	-0.222	Destabilizing	0.024	N	0.178	neutral	None	None	None	None	N
N/V	0.7793	likely_pathogenic	0.8584	pathogenic	0.142	Stabilizing	0.072	N	0.476	neutral	None	None	None	None	N
N/W	0.9435	likely_pathogenic	0.9608	pathogenic	-0.452	Destabilizing	0.676	D	0.423	neutral	None	None	None	None	N
N/Y	0.342	ambiguous	0.4024	ambiguous	-0.154	Destabilizing	None	N	0.213	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.