TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14586	43981;43982;43983	chr2:178631292;178631291;178631290	chr2:179496019;179496018;179496017
N2AB	12945	39058;39059;39060	chr2:178631292;178631291;178631290	chr2:179496019;179496018;179496017
N2A	12018	36277;36278;36279	chr2:178631292;178631291;178631290	chr2:179496019;179496018;179496017
N2B	5521	16786;16787;16788	chr2:178631292;178631291;178631290	chr2:179496019;179496018;179496017
Novex-1	5646	17161;17162;17163	chr2:178631292;178631291;178631290	chr2:179496019;179496018;179496017
Novex-2	5713	17362;17363;17364	chr2:178631292;178631291;178631290	chr2:179496019;179496018;179496017
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-97
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.8537
• 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	rs2059766641	None	0.98	D	0.635	0.56	0.564208378351	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/A	rs2059766641	None	0.98	D	0.635	0.56	0.564208378351	gnomAD-4.0.0	5.17106E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.62015E-06	0	0
P/T	None	None	0.98	D	0.69	0.561	0.761402108219	gnomAD-4.0.0	1.60865E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.97714E-05	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
P/A	0.1769	likely_benign	0.1614	benign	-1.261	Destabilizing	0.98	D	0.635	neutral	D	0.64362078	None	None	N
P/C	0.7866	likely_pathogenic	0.7999	pathogenic	-0.71	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
P/D	0.8662	likely_pathogenic	0.8898	pathogenic	-0.741	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
P/E	0.7534	likely_pathogenic	0.7724	pathogenic	-0.76	Destabilizing	0.999	D	0.678	prob.neutral	None	None	None	None	N
P/F	0.8742	likely_pathogenic	0.8798	pathogenic	-1.008	Destabilizing	0.996	D	0.711	prob.delet.	None	None	None	None	N
P/G	0.7584	likely_pathogenic	0.7832	pathogenic	-1.557	Destabilizing	0.999	D	0.658	neutral	None	None	None	None	N
P/H	0.6101	likely_pathogenic	0.6449	pathogenic	-1.071	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
P/I	0.5517	ambiguous	0.4833	ambiguous	-0.565	Destabilizing	0.971	D	0.695	prob.neutral	None	None	None	None	N
P/K	0.8073	likely_pathogenic	0.8341	pathogenic	-0.929	Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	N
P/L	0.2656	likely_benign	0.2482	benign	-0.565	Destabilizing	0.135	N	0.607	neutral	D	0.681556648	None	None	N
P/M	0.7208	likely_pathogenic	0.7122	pathogenic	-0.383	Destabilizing	0.996	D	0.671	neutral	None	None	None	None	N
P/N	0.796	likely_pathogenic	0.809	pathogenic	-0.642	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
P/Q	0.6165	likely_pathogenic	0.6412	pathogenic	-0.813	Destabilizing	0.999	D	0.695	prob.neutral	D	0.754613751	None	None	N
P/R	0.5807	likely_pathogenic	0.6186	pathogenic	-0.438	Destabilizing	0.999	D	0.675	prob.neutral	D	0.754613751	None	None	N
P/S	0.3647	ambiguous	0.3771	ambiguous	-1.187	Destabilizing	0.997	D	0.69	prob.neutral	D	0.755415398	None	None	N
P/T	0.2427	likely_benign	0.2318	benign	-1.094	Destabilizing	0.98	D	0.69	prob.neutral	D	0.697021499	None	None	N
P/V	0.432	ambiguous	0.3771	ambiguous	-0.761	Destabilizing	0.469	N	0.621	neutral	None	None	None	None	N
P/W	0.9378	likely_pathogenic	0.9482	pathogenic	-1.165	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
P/Y	0.8428	likely_pathogenic	0.8584	pathogenic	-0.872	Destabilizing	0.999	D	0.708	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.