TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22583	67972;67973;67974	chr2:178579283;178579282;178579281	chr2:179444010;179444009;179444008
N2AB	20942	63049;63050;63051	chr2:178579283;178579282;178579281	chr2:179444010;179444009;179444008
N2A	20015	60268;60269;60270	chr2:178579283;178579282;178579281	chr2:179444010;179444009;179444008
N2B	13518	40777;40778;40779	chr2:178579283;178579282;178579281	chr2:179444010;179444009;179444008
Novex-1	13643	41152;41153;41154	chr2:178579283;178579282;178579281	chr2:179444010;179444009;179444008
Novex-2	13710	41353;41354;41355	chr2:178579283;178579282;178579281	chr2:179444010;179444009;179444008
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-127
• Domain position: 24
• Structural Position: 47
• Q(SASA): 0.3162
• 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/Y	None	None	0.295	D	0.578	0.273	0.545739167163	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
S/A	0.0891	likely_benign	0.085	benign	-0.543	Destabilizing	0.005	N	0.365	neutral	D	0.538025434	None	None	N
S/C	0.0905	likely_benign	0.0935	benign	-0.464	Destabilizing	0.295	N	0.527	neutral	N	0.499956513	None	None	N
S/D	0.348	ambiguous	0.3086	benign	-0.023	Destabilizing	0.072	N	0.357	neutral	None	None	None	None	N
S/E	0.3927	ambiguous	0.3499	ambiguous	-0.029	Destabilizing	0.072	N	0.34	neutral	None	None	None	None	N
S/F	0.1254	likely_benign	0.107	benign	-0.831	Destabilizing	0.055	N	0.581	neutral	D	0.535545276	None	None	N
S/G	0.1203	likely_benign	0.1195	benign	-0.775	Destabilizing	0.031	N	0.326	neutral	None	None	None	None	N
S/H	0.2361	likely_benign	0.2259	benign	-1.213	Destabilizing	0.628	D	0.521	neutral	None	None	None	None	N
S/I	0.0904	likely_benign	0.0805	benign	-0.042	Destabilizing	None	N	0.299	neutral	None	None	None	None	N
S/K	0.5506	ambiguous	0.4888	ambiguous	-0.58	Destabilizing	0.072	N	0.343	neutral	None	None	None	None	N
S/L	0.0739	likely_benign	0.0695	benign	-0.042	Destabilizing	None	N	0.301	neutral	None	None	None	None	N
S/M	0.1228	likely_benign	0.1152	benign	0.023	Stabilizing	0.214	N	0.525	neutral	None	None	None	None	N
S/N	0.1192	likely_benign	0.1101	benign	-0.605	Destabilizing	0.072	N	0.372	neutral	None	None	None	None	N
S/P	0.8838	likely_pathogenic	0.8583	pathogenic	-0.175	Destabilizing	0.106	N	0.532	neutral	N	0.517389205	None	None	N
S/Q	0.3602	ambiguous	0.3251	benign	-0.684	Destabilizing	0.356	N	0.451	neutral	None	None	None	None	N
S/R	0.4562	ambiguous	0.3993	ambiguous	-0.489	Destabilizing	0.072	N	0.539	neutral	None	None	None	None	N
S/T	0.0565	likely_benign	0.0544	benign	-0.58	Destabilizing	None	N	0.135	neutral	N	0.421873054	None	None	N
S/V	0.1069	likely_benign	0.0983	benign	-0.175	Destabilizing	0.007	N	0.428	neutral	None	None	None	None	N
S/W	0.2737	likely_benign	0.2524	benign	-0.865	Destabilizing	0.864	D	0.581	neutral	None	None	None	None	N
S/Y	0.1528	likely_benign	0.1403	benign	-0.559	Destabilizing	0.295	N	0.578	neutral	D	0.531774252	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.