TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9996	30211;30212;30213	chr2:178704384;178704383;178704382	chr2:179569111;179569110;179569109
N2AB	9679	29260;29261;29262	chr2:178704384;178704383;178704382	chr2:179569111;179569110;179569109
N2A	8752	26479;26480;26481	chr2:178704384;178704383;178704382	chr2:179569111;179569110;179569109
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: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-85
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.6699
• 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
Q/P	None	None	0.966	None	0.385	0.344	0.497086342495	gnomAD-4.0.0	6.84327E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99649E-07	0	0
Q/R	None	None	0.012	None	0.157	0.137	0.176091768786	gnomAD-4.0.0	6.84327E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99649E-07	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
Q/A	0.3034	likely_benign	0.3251	benign	-0.213	Destabilizing	0.688	D	0.343	neutral	None	None	None	None	N
Q/C	0.8446	likely_pathogenic	0.8719	pathogenic	0.146	Stabilizing	0.998	D	0.351	neutral	None	None	None	None	N
Q/D	0.4529	ambiguous	0.4854	ambiguous	-0.034	Destabilizing	0.728	D	0.335	neutral	None	None	None	None	N
Q/E	0.0846	likely_benign	0.0801	benign	-0.049	Destabilizing	0.051	N	0.087	neutral	None	None	None	None	N
Q/F	0.8268	likely_pathogenic	0.8607	pathogenic	-0.327	Destabilizing	0.974	D	0.359	neutral	None	None	None	None	N
Q/G	0.3706	ambiguous	0.3873	ambiguous	-0.425	Destabilizing	0.842	D	0.369	neutral	None	None	None	None	N
Q/H	0.2821	likely_benign	0.329	benign	-0.308	Destabilizing	0.028	N	0.185	neutral	None	None	None	None	N
Q/I	0.597	likely_pathogenic	0.6289	pathogenic	0.264	Stabilizing	0.974	D	0.376	neutral	None	None	None	None	N
Q/K	0.0987	likely_benign	0.0965	benign	0.002	Stabilizing	0.012	N	0.092	neutral	None	None	None	None	N
Q/L	0.2173	likely_benign	0.2337	benign	0.264	Stabilizing	0.801	D	0.357	neutral	None	None	None	None	N
Q/M	0.5393	ambiguous	0.5699	pathogenic	0.445	Stabilizing	0.991	D	0.367	neutral	None	None	None	None	N
Q/N	0.3625	ambiguous	0.4038	ambiguous	-0.318	Destabilizing	0.842	D	0.311	neutral	None	None	None	None	N
Q/P	0.3091	likely_benign	0.3168	benign	0.134	Stabilizing	0.966	D	0.385	neutral	None	None	None	None	N
Q/R	0.1203	likely_benign	0.1253	benign	0.147	Stabilizing	0.012	N	0.157	neutral	None	None	None	None	N
Q/S	0.3325	likely_benign	0.3687	ambiguous	-0.31	Destabilizing	0.842	D	0.341	neutral	None	None	None	None	N
Q/T	0.2923	likely_benign	0.3073	benign	-0.166	Destabilizing	0.842	D	0.352	neutral	None	None	None	None	N
Q/V	0.4091	ambiguous	0.4421	ambiguous	0.134	Stabilizing	0.915	D	0.365	neutral	None	None	None	None	N
Q/W	0.6807	likely_pathogenic	0.7147	pathogenic	-0.294	Destabilizing	0.998	D	0.375	neutral	None	None	None	None	N
Q/Y	0.6407	likely_pathogenic	0.6966	pathogenic	-0.047	Destabilizing	0.949	D	0.377	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.