TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9738	29437;29438;29439	chr2:178706662;178706661;178706660	chr2:179571389;179571388;179571387
N2AB	9421	28486;28487;28488	chr2:178706662;178706661;178706660	chr2:179571389;179571388;179571387
N2A	8494	25705;25706;25707	chr2:178706662;178706661;178706660	chr2:179571389;179571388;179571387
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-83
• Domain position: 41
• Structural Position: 56
• Q(SASA): 0.667
• 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/R	rs1370390355	0.28	0.997	None	0.573	0.402	0.363751660372	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
Q/R	rs1370390355	0.28	0.997	None	0.573	0.402	0.363751660372	gnomAD-4.0.0	1.59106E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43287E-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
Q/A	0.5861	likely_pathogenic	0.44	ambiguous	-0.253	Destabilizing	0.997	D	0.555	neutral	None	None	None	None	N
Q/C	0.9838	likely_pathogenic	0.952	pathogenic	0.227	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
Q/D	0.9534	likely_pathogenic	0.8638	pathogenic	0.074	Stabilizing	0.997	D	0.578	neutral	None	None	None	None	N
Q/E	0.3735	ambiguous	0.2154	benign	0.064	Stabilizing	0.992	D	0.454	neutral	None	None	None	None	N
Q/F	0.9577	likely_pathogenic	0.8913	pathogenic	-0.338	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
Q/G	0.835	likely_pathogenic	0.6847	pathogenic	-0.475	Destabilizing	0.997	D	0.572	neutral	None	None	None	None	N
Q/H	0.8313	likely_pathogenic	0.6253	pathogenic	-0.339	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	N
Q/I	0.7086	likely_pathogenic	0.5459	ambiguous	0.251	Stabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
Q/K	0.4263	ambiguous	0.2629	benign	0.004	Stabilizing	0.997	D	0.538	neutral	None	None	None	None	N
Q/L	0.4399	ambiguous	0.2821	benign	0.251	Stabilizing	0.997	D	0.572	neutral	None	None	None	None	N
Q/M	0.6193	likely_pathogenic	0.5247	ambiguous	0.485	Stabilizing	0.999	D	0.65	neutral	None	None	None	None	N
Q/N	0.7627	likely_pathogenic	0.6173	pathogenic	-0.263	Destabilizing	0.999	D	0.619	neutral	None	None	None	None	N
Q/P	0.4415	ambiguous	0.2503	benign	0.112	Stabilizing	0.999	D	0.712	prob.delet.	None	None	None	None	N
Q/R	0.5385	ambiguous	0.3418	ambiguous	0.15	Stabilizing	0.997	D	0.573	neutral	None	None	None	None	N
Q/S	0.6728	likely_pathogenic	0.5482	ambiguous	-0.297	Destabilizing	0.997	D	0.535	neutral	None	None	None	None	N
Q/T	0.5744	likely_pathogenic	0.4612	ambiguous	-0.147	Destabilizing	0.999	D	0.644	neutral	None	None	None	None	N
Q/V	0.5767	likely_pathogenic	0.4267	ambiguous	0.112	Stabilizing	0.999	D	0.612	neutral	None	None	None	None	N
Q/W	0.9706	likely_pathogenic	0.9018	pathogenic	-0.302	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
Q/Y	0.9435	likely_pathogenic	0.8288	pathogenic	-0.064	Destabilizing	0.999	D	0.705	prob.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.