TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6488	19687;19688;19689	chr2:178728362;178728361;178728360	chr2:179593089;179593088;179593087
N2AB	6171	18736;18737;18738	chr2:178728362;178728361;178728360	chr2:179593089;179593088;179593087
N2A	5244	15955;15956;15957	chr2:178728362;178728361;178728360	chr2:179593089;179593088;179593087
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: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-49
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.6427
• 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
T/N	rs2079735151	None	0.096	N	0.221	0.075	0.227260227426	gnomAD-4.0.0	1.61567E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.88807E-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
T/A	0.076	likely_benign	0.0834	benign	-0.168	Destabilizing	0.019	N	0.147	neutral	N	0.459407147	None	None	N
T/C	0.3655	ambiguous	0.4836	ambiguous	-0.307	Destabilizing	0.883	D	0.344	neutral	None	None	None	None	N
T/D	0.305	likely_benign	0.3578	ambiguous	0.136	Stabilizing	0.124	N	0.345	neutral	None	None	None	None	N
T/E	0.2119	likely_benign	0.2353	benign	0.049	Stabilizing	0.004	N	0.196	neutral	None	None	None	None	N
T/F	0.1918	likely_benign	0.243	benign	-0.765	Destabilizing	0.497	N	0.419	neutral	None	None	None	None	N
T/G	0.1632	likely_benign	0.2106	benign	-0.255	Destabilizing	0.124	N	0.353	neutral	None	None	None	None	N
T/H	0.1781	likely_benign	0.2265	benign	-0.439	Destabilizing	0.667	D	0.363	neutral	None	None	None	None	N
T/I	0.1363	likely_benign	0.1747	benign	-0.065	Destabilizing	0.096	N	0.321	neutral	N	0.507681097	None	None	N
T/K	0.1363	likely_benign	0.1521	benign	-0.272	Destabilizing	0.055	N	0.316	neutral	None	None	None	None	N
T/L	0.081	likely_benign	0.0913	benign	-0.065	Destabilizing	None	N	0.162	neutral	None	None	None	None	N
T/M	0.0812	likely_benign	0.0887	benign	-0.093	Destabilizing	0.025	N	0.208	neutral	None	None	None	None	N
T/N	0.0909	likely_benign	0.1139	benign	-0.059	Destabilizing	0.096	N	0.221	neutral	N	0.475742037	None	None	N
T/P	0.117	likely_benign	0.1135	benign	-0.073	Destabilizing	0.001	N	0.249	neutral	N	0.494847873	None	None	N
T/Q	0.1389	likely_benign	0.1559	benign	-0.268	Destabilizing	0.22	N	0.395	neutral	None	None	None	None	N
T/R	0.1055	likely_benign	0.1198	benign	0.016	Stabilizing	0.001	N	0.193	neutral	None	None	None	None	N
T/S	0.0845	likely_benign	0.1041	benign	-0.238	Destabilizing	0.001	N	0.144	neutral	N	0.424523783	None	None	N
T/V	0.1145	likely_benign	0.1365	benign	-0.073	Destabilizing	0.004	N	0.105	neutral	None	None	None	None	N
T/W	0.4379	ambiguous	0.4992	ambiguous	-0.837	Destabilizing	0.958	D	0.365	neutral	None	None	None	None	N
T/Y	0.2139	likely_benign	0.263	benign	-0.519	Destabilizing	0.859	D	0.382	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.