TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7521	22786;22787;22788	chr2:178722102;178722101;178722100	chr2:179586829;179586828;179586827
N2AB	7204	21835;21836;21837	chr2:178722102;178722101;178722100	chr2:179586829;179586828;179586827
N2A	6277	19054;19055;19056	chr2:178722102;178722101;178722100	chr2:179586829;179586828;179586827
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: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-60
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.1819
• 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
P/A	rs752570029	None	0.005	N	0.385	0.296	0.184867976434	gnomAD-4.0.0	6.99683E-07	None	None	None	None	N	None	0	2.5137E-05	None	0	0	None	0	0	0	0	0
P/L	None	None	0.063	N	0.505	0.279	0.336892272479	gnomAD-4.0.0	6.99264E-07	None	None	None	None	N	None	3.11585E-05	0	None	0	0	None	0	0	0	0	0
P/S	rs752570029	-1.235	0.358	N	0.416	0.301	0.203808441222	gnomAD-2.1.1	4.44E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.55E-06	0
P/T	None	None	0.079	N	0.417	0.286	0.215109475489	gnomAD-4.0.0	6.99684E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.12204E-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
P/A	0.2186	likely_benign	0.3418	ambiguous	-1.575	Destabilizing	0.005	N	0.385	neutral	N	0.472345246	None	None	N
P/C	0.9243	likely_pathogenic	0.9624	pathogenic	-1.018	Destabilizing	0.998	D	0.681	prob.neutral	None	None	None	None	N
P/D	0.98	likely_pathogenic	0.9898	pathogenic	-1.394	Destabilizing	0.574	D	0.633	neutral	None	None	None	None	N
P/E	0.9355	likely_pathogenic	0.964	pathogenic	-1.337	Destabilizing	0.681	D	0.597	neutral	None	None	None	None	N
P/F	0.9679	likely_pathogenic	0.9869	pathogenic	-1.089	Destabilizing	0.996	D	0.721	prob.delet.	None	None	None	None	N
P/G	0.8238	likely_pathogenic	0.9107	pathogenic	-1.962	Destabilizing	0.873	D	0.592	neutral	None	None	None	None	N
P/H	0.9454	likely_pathogenic	0.9759	pathogenic	-1.566	Destabilizing	0.999	D	0.641	neutral	N	0.491716949	None	None	N
P/I	0.6927	likely_pathogenic	0.8145	pathogenic	-0.584	Destabilizing	0.971	D	0.651	neutral	None	None	None	None	N
P/K	0.9783	likely_pathogenic	0.9887	pathogenic	-1.251	Destabilizing	0.986	D	0.594	neutral	None	None	None	None	N
P/L	0.3232	likely_benign	0.4865	ambiguous	-0.584	Destabilizing	0.063	N	0.505	neutral	N	0.403720783	None	None	N
P/M	0.7314	likely_pathogenic	0.8407	pathogenic	-0.443	Destabilizing	0.989	D	0.648	neutral	None	None	None	None	N
P/N	0.944	likely_pathogenic	0.9738	pathogenic	-1.121	Destabilizing	0.967	D	0.691	prob.neutral	None	None	None	None	N
P/Q	0.9014	likely_pathogenic	0.9494	pathogenic	-1.203	Destabilizing	0.995	D	0.708	prob.delet.	None	None	None	None	N
P/R	0.9504	likely_pathogenic	0.976	pathogenic	-0.852	Destabilizing	0.997	D	0.697	prob.neutral	N	0.477220318	None	None	N
P/S	0.722	likely_pathogenic	0.8574	pathogenic	-1.714	Destabilizing	0.358	N	0.416	neutral	N	0.47078831	None	None	N
P/T	0.4137	ambiguous	0.6045	pathogenic	-1.536	Destabilizing	0.079	N	0.417	neutral	N	0.47078831	None	None	N
P/V	0.4945	ambiguous	0.6716	pathogenic	-0.88	Destabilizing	0.711	D	0.573	neutral	None	None	None	None	N
P/W	0.9924	likely_pathogenic	0.9972	pathogenic	-1.372	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
P/Y	0.9816	likely_pathogenic	0.9924	pathogenic	-1.041	Destabilizing	0.999	D	0.715	prob.delet.	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.