TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6497	19714;19715;19716	chr2:178728335;178728334;178728333	chr2:179593062;179593061;179593060
N2AB	6180	18763;18764;18765	chr2:178728335;178728334;178728333	chr2:179593062;179593061;179593060
N2A	5253	15982;15983;15984	chr2:178728335;178728334;178728333	chr2:179593062;179593061;179593060
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: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-49
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.3557
• 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/C	None	None	0.999	N	0.344	0.36	0.400468435593	gnomAD-4.0.0	2.74095E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	3.49284E-05	1.65926E-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	0.0766	likely_benign	0.0826	benign	-0.616	Destabilizing	0.826	D	0.331	neutral	N	0.463645059	None	None	N
S/C	0.1604	likely_benign	0.1801	benign	-0.372	Destabilizing	0.999	D	0.344	neutral	N	0.491664042	None	None	N
S/D	0.3424	ambiguous	0.4068	ambiguous	-0.024	Destabilizing	0.884	D	0.231	neutral	None	None	None	None	N
S/E	0.4584	ambiguous	0.5361	ambiguous	-0.07	Destabilizing	0.939	D	0.227	neutral	None	None	None	None	N
S/F	0.1871	likely_benign	0.1992	benign	-1.017	Destabilizing	0.015	N	0.233	neutral	N	0.46145624	None	None	N
S/G	0.1146	likely_benign	0.1228	benign	-0.809	Destabilizing	0.863	D	0.279	neutral	None	None	None	None	N
S/H	0.3076	likely_benign	0.3723	ambiguous	-1.326	Destabilizing	0.991	D	0.365	neutral	None	None	None	None	N
S/I	0.1886	likely_benign	0.2063	benign	-0.224	Destabilizing	0.939	D	0.361	neutral	None	None	None	None	N
S/K	0.5376	ambiguous	0.643	pathogenic	-0.593	Destabilizing	0.939	D	0.226	neutral	None	None	None	None	N
S/L	0.1016	likely_benign	0.1115	benign	-0.224	Destabilizing	0.759	D	0.376	neutral	None	None	None	None	N
S/M	0.2306	likely_benign	0.2515	benign	0.114	Stabilizing	0.997	D	0.359	neutral	None	None	None	None	N
S/N	0.1426	likely_benign	0.1653	benign	-0.431	Destabilizing	0.17	N	0.135	neutral	None	None	None	None	N
S/P	0.1178	likely_benign	0.1569	benign	-0.323	Destabilizing	0.996	D	0.372	neutral	N	0.453894915	None	None	N
S/Q	0.4298	ambiguous	0.5164	ambiguous	-0.638	Destabilizing	0.991	D	0.362	neutral	None	None	None	None	N
S/R	0.4473	ambiguous	0.5314	ambiguous	-0.427	Destabilizing	0.991	D	0.375	neutral	None	None	None	None	N
S/T	0.0801	likely_benign	0.0867	benign	-0.5	Destabilizing	0.134	N	0.101	neutral	N	0.50228748	None	None	N
S/V	0.1723	likely_benign	0.1868	benign	-0.323	Destabilizing	0.939	D	0.357	neutral	None	None	None	None	N
S/W	0.3174	likely_benign	0.3376	benign	-0.985	Destabilizing	0.999	D	0.416	neutral	None	None	None	None	N
S/Y	0.1804	likely_benign	0.1948	benign	-0.721	Destabilizing	0.953	D	0.401	neutral	N	0.496183493	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.