TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33315	100168;100169;100170	chr2:178537166;178537165;178537164	chr2:179401893;179401892;179401891
N2AB	31674	95245;95246;95247	chr2:178537166;178537165;178537164	chr2:179401893;179401892;179401891
N2A	30747	92464;92465;92466	chr2:178537166;178537165;178537164	chr2:179401893;179401892;179401891
N2B	24250	72973;72974;72975	chr2:178537166;178537165;178537164	chr2:179401893;179401892;179401891
Novex-1	24375	73348;73349;73350	chr2:178537166;178537165;178537164	chr2:179401893;179401892;179401891
Novex-2	24442	73549;73550;73551	chr2:178537166;178537165;178537164	chr2:179401893;179401892;179401891
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-130
• Domain position: 26
• Structural Position: 27
• Q(SASA): 0.1586
• 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/T	rs1401105733	-2.039	0.998	D	0.803	0.529	0.51230852224	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
P/T	rs1401105733	-2.039	0.998	D	0.803	0.529	0.51230852224	gnomAD-4.0.0	1.5916E-06	None	None	None	None	N	None	5.65867E-05	0	None	0	0	None	0	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	0.7778	likely_pathogenic	0.7548	pathogenic	-2.037	Highly Destabilizing	0.992	D	0.718	prob.delet.	N	0.518134949	None	None	N
P/C	0.9772	likely_pathogenic	0.9785	pathogenic	-1.462	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
P/D	0.9983	likely_pathogenic	0.9982	pathogenic	-2.708	Highly Destabilizing	0.999	D	0.812	deleterious	None	None	None	None	N
P/E	0.9963	likely_pathogenic	0.9955	pathogenic	-2.651	Highly Destabilizing	0.999	D	0.81	deleterious	None	None	None	None	N
P/F	0.9992	likely_pathogenic	0.999	pathogenic	-1.593	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
P/G	0.9849	likely_pathogenic	0.9833	pathogenic	-2.43	Highly Destabilizing	0.997	D	0.813	deleterious	None	None	None	None	N
P/H	0.9961	likely_pathogenic	0.9945	pathogenic	-2.149	Highly Destabilizing	1.0	D	0.89	deleterious	D	0.557003259	None	None	N
P/I	0.9916	likely_pathogenic	0.9895	pathogenic	-1.003	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
P/K	0.9983	likely_pathogenic	0.9974	pathogenic	-1.839	Destabilizing	0.999	D	0.814	deleterious	None	None	None	None	N
P/L	0.9672	likely_pathogenic	0.9562	pathogenic	-1.003	Destabilizing	0.999	D	0.891	deleterious	D	0.555228832	None	None	N
P/M	0.9947	likely_pathogenic	0.9937	pathogenic	-0.681	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
P/N	0.9978	likely_pathogenic	0.9977	pathogenic	-1.791	Destabilizing	0.999	D	0.894	deleterious	None	None	None	None	N
P/Q	0.9947	likely_pathogenic	0.9925	pathogenic	-1.901	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
P/R	0.9944	likely_pathogenic	0.9904	pathogenic	-1.321	Destabilizing	0.999	D	0.88	deleterious	D	0.524655862	None	None	N
P/S	0.9664	likely_pathogenic	0.9608	pathogenic	-2.251	Highly Destabilizing	0.957	D	0.571	neutral	N	0.503398056	None	None	N
P/T	0.9577	likely_pathogenic	0.9534	pathogenic	-2.086	Highly Destabilizing	0.998	D	0.803	deleterious	D	0.529744744	None	None	N
P/V	0.9616	likely_pathogenic	0.9564	pathogenic	-1.318	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
P/W	0.9998	likely_pathogenic	0.9997	pathogenic	-1.979	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
P/Y	0.9994	likely_pathogenic	0.9992	pathogenic	-1.689	Destabilizing	1.0	D	0.908	deleterious	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.