TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6293	19102;19103;19104	chr2:178729161;178729160;178729159	chr2:179593888;179593887;179593886
N2AB	5976	18151;18152;18153	chr2:178729161;178729160;178729159	chr2:179593888;179593887;179593886
N2A	5049	15370;15371;15372	chr2:178729161;178729160;178729159	chr2:179593888;179593887;179593886
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: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-47
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.3872
• 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/P	rs1560769509	None	0.921	N	0.379	0.387	0.305086939656	gnomAD-4.0.0	2.10097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.82503E-06	0	1.69733E-05

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	0.0812	likely_benign	0.0738	benign	-0.425	Destabilizing	0.089	N	0.177	neutral	N	0.505814228	None	None	N
S/C	0.1251	likely_benign	0.1294	benign	-0.355	Destabilizing	0.983	D	0.325	neutral	None	None	None	None	N
S/D	0.5412	ambiguous	0.5445	ambiguous	0.422	Stabilizing	0.593	D	0.31	neutral	None	None	None	None	N
S/E	0.5356	ambiguous	0.5674	pathogenic	0.404	Stabilizing	0.593	D	0.232	neutral	None	None	None	None	N
S/F	0.1517	likely_benign	0.1495	benign	-0.788	Destabilizing	0.264	N	0.365	neutral	None	None	None	None	N
S/G	0.1207	likely_benign	0.1121	benign	-0.626	Destabilizing	0.593	D	0.229	neutral	None	None	None	None	N
S/H	0.2873	likely_benign	0.3146	benign	-0.96	Destabilizing	0.836	D	0.331	neutral	None	None	None	None	N
S/I	0.1336	likely_benign	0.1328	benign	-0.011	Destabilizing	0.129	N	0.321	neutral	None	None	None	None	N
S/K	0.5385	ambiguous	0.5849	pathogenic	-0.314	Destabilizing	0.593	D	0.236	neutral	None	None	None	None	N
S/L	0.0873	likely_benign	0.0849	benign	-0.011	Destabilizing	0.001	N	0.26	neutral	N	0.483846359	None	None	N
S/M	0.1939	likely_benign	0.1916	benign	-0.074	Destabilizing	0.716	D	0.343	neutral	None	None	None	None	N
S/N	0.1786	likely_benign	0.1757	benign	-0.273	Destabilizing	0.593	D	0.335	neutral	None	None	None	None	N
S/P	0.8956	likely_pathogenic	0.8649	pathogenic	-0.116	Destabilizing	0.921	D	0.379	neutral	N	0.485910274	None	None	N
S/Q	0.4092	ambiguous	0.445	ambiguous	-0.349	Destabilizing	0.94	D	0.373	neutral	None	None	None	None	N
S/R	0.4019	ambiguous	0.4482	ambiguous	-0.226	Destabilizing	0.836	D	0.391	neutral	None	None	None	None	N
S/T	0.0714	likely_benign	0.067	benign	-0.318	Destabilizing	0.003	N	0.101	neutral	N	0.44645928	None	None	N
S/V	0.1317	likely_benign	0.1286	benign	-0.116	Destabilizing	0.01	N	0.301	neutral	None	None	None	None	N
S/W	0.3641	ambiguous	0.3825	ambiguous	-0.83	Destabilizing	0.983	D	0.402	neutral	None	None	None	None	N
S/Y	0.1696	likely_benign	0.169	benign	-0.505	Destabilizing	0.01	N	0.279	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.