TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6803	20632;20633;20634	chr2:178725915;178725914;178725913	chr2:179590642;179590641;179590640
N2AB	6486	19681;19682;19683	chr2:178725915;178725914;178725913	chr2:179590642;179590641;179590640
N2A	5559	16900;16901;16902	chr2:178725915;178725914;178725913	chr2:179590642;179590641;179590640
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: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-52
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.5678
• 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
S/I	rs2079258083	None	0.998	N	0.405	0.523	0.734682175585	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
S/I	rs2079258083	None	0.998	N	0.405	0.523	0.734682175585	gnomAD-4.0.0	6.57618E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47033E-05	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
S/A	0.1296	likely_benign	0.1277	benign	-0.21	Destabilizing	0.17	N	0.248	neutral	None	None	None	None	N
S/C	0.304	likely_benign	0.3895	ambiguous	-0.353	Destabilizing	0.998	D	0.389	neutral	D	0.539341347	None	None	N
S/D	0.7497	likely_pathogenic	0.7055	pathogenic	0.535	Stabilizing	0.021	N	0.072	neutral	None	None	None	None	N
S/E	0.8339	likely_pathogenic	0.8273	pathogenic	0.452	Stabilizing	0.112	N	0.087	neutral	None	None	None	None	N
S/F	0.4224	ambiguous	0.4293	ambiguous	-0.872	Destabilizing	0.998	D	0.391	neutral	None	None	None	None	N
S/G	0.1241	likely_benign	0.1127	benign	-0.303	Destabilizing	0.795	D	0.249	neutral	N	0.492572999	None	None	N
S/H	0.6605	likely_pathogenic	0.6651	pathogenic	-0.718	Destabilizing	0.994	D	0.377	neutral	None	None	None	None	N
S/I	0.3163	likely_benign	0.3255	benign	-0.102	Destabilizing	0.998	D	0.405	neutral	N	0.501802937	None	None	N
S/K	0.9303	likely_pathogenic	0.9305	pathogenic	-0.23	Destabilizing	0.962	D	0.173	neutral	None	None	None	None	N
S/L	0.1793	likely_benign	0.1751	benign	-0.102	Destabilizing	0.981	D	0.361	neutral	None	None	None	None	N
S/M	0.3383	likely_benign	0.3394	benign	-0.127	Destabilizing	1.0	D	0.372	neutral	None	None	None	None	N
S/N	0.2308	likely_benign	0.1853	benign	-0.093	Destabilizing	0.008	N	0.098	neutral	N	0.487039591	None	None	N
S/P	0.1803	likely_benign	0.1672	benign	-0.11	Destabilizing	0.009	N	0.134	neutral	None	None	None	None	N
S/Q	0.7779	likely_pathogenic	0.7779	pathogenic	-0.242	Destabilizing	0.962	D	0.277	neutral	None	None	None	None	N
S/R	0.9123	likely_pathogenic	0.9111	pathogenic	-0.115	Destabilizing	0.95	D	0.407	neutral	N	0.499143138	None	None	N
S/T	0.1265	likely_benign	0.1176	benign	-0.188	Destabilizing	0.197	N	0.224	neutral	N	0.489988878	None	None	N
S/V	0.3362	likely_benign	0.3307	benign	-0.11	Destabilizing	0.95	D	0.383	neutral	None	None	None	None	N
S/W	0.6019	likely_pathogenic	0.6362	pathogenic	-0.935	Destabilizing	1.0	D	0.491	neutral	None	None	None	None	N
S/Y	0.3644	ambiguous	0.3817	ambiguous	-0.604	Destabilizing	0.998	D	0.392	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.