TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7679	23260;23261;23262	chr2:178720984;178720983;178720982	chr2:179585711;179585710;179585709
N2AB	7362	22309;22310;22311	chr2:178720984;178720983;178720982	chr2:179585711;179585710;179585709
N2A	6435	19528;19529;19530	chr2:178720984;178720983;178720982	chr2:179585711;179585710;179585709
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: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-61
• Domain position: 72
• Structural Position: 154
• Q(SASA): 0.1394
• 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
Y/S	rs1052929607	None	1.0	D	0.908	0.825	0.884691997466	gnomAD-4.0.0	6.00162E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56252E-06	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
Y/A	0.9909	likely_pathogenic	0.9926	pathogenic	-2.784	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
Y/C	0.8977	likely_pathogenic	0.9111	pathogenic	-2.145	Highly Destabilizing	1.0	D	0.891	deleterious	D	0.665728122	None	None	N
Y/D	0.9948	likely_pathogenic	0.9962	pathogenic	-3.299	Highly Destabilizing	1.0	D	0.909	deleterious	D	0.665728122	None	None	N
Y/E	0.9984	likely_pathogenic	0.9989	pathogenic	-3.052	Highly Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	N
Y/F	0.1132	likely_benign	0.1333	benign	-1.13	Destabilizing	0.999	D	0.691	prob.neutral	D	0.581554153	None	None	N
Y/G	0.9895	likely_pathogenic	0.9901	pathogenic	-3.247	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
Y/H	0.9591	likely_pathogenic	0.9709	pathogenic	-2.41	Highly Destabilizing	1.0	D	0.809	deleterious	D	0.665526318	None	None	N
Y/I	0.754	likely_pathogenic	0.8208	pathogenic	-1.24	Destabilizing	0.999	D	0.865	deleterious	None	None	None	None	N
Y/K	0.9983	likely_pathogenic	0.9988	pathogenic	-2.265	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
Y/L	0.7265	likely_pathogenic	0.76	pathogenic	-1.24	Destabilizing	0.997	D	0.796	deleterious	None	None	None	None	N
Y/M	0.9337	likely_pathogenic	0.9485	pathogenic	-1.313	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
Y/N	0.974	likely_pathogenic	0.9799	pathogenic	-3.189	Highly Destabilizing	1.0	D	0.907	deleterious	D	0.665728122	None	None	N
Y/P	0.9989	likely_pathogenic	0.9991	pathogenic	-1.772	Destabilizing	1.0	D	0.924	deleterious	None	None	None	None	N
Y/Q	0.9979	likely_pathogenic	0.9986	pathogenic	-2.771	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
Y/R	0.9937	likely_pathogenic	0.9954	pathogenic	-2.368	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
Y/S	0.9792	likely_pathogenic	0.9836	pathogenic	-3.548	Highly Destabilizing	1.0	D	0.908	deleterious	D	0.665728122	None	None	N
Y/T	0.9868	likely_pathogenic	0.9904	pathogenic	-3.152	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
Y/V	0.7316	likely_pathogenic	0.7917	pathogenic	-1.772	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
Y/W	0.7978	likely_pathogenic	0.8161	pathogenic	-0.461	Destabilizing	1.0	D	0.8	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.