TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26641	80146;80147;80148	chr2:178566211;178566210;178566209	chr2:179430938;179430937;179430936
N2AB	25000	75223;75224;75225	chr2:178566211;178566210;178566209	chr2:179430938;179430937;179430936
N2A	24073	72442;72443;72444	chr2:178566211;178566210;178566209	chr2:179430938;179430937;179430936
N2B	17576	52951;52952;52953	chr2:178566211;178566210;178566209	chr2:179430938;179430937;179430936
Novex-1	17701	53326;53327;53328	chr2:178566211;178566210;178566209	chr2:179430938;179430937;179430936
Novex-2	17768	53527;53528;53529	chr2:178566211;178566210;178566209	chr2:179430938;179430937;179430936
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-138
• Domain position: 48
• Structural Position: 127
• Q(SASA): 0.6076
• 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
K/N	rs745463486	0.102	0.801	N	0.415	0.158	0.253205268125	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
K/N	rs745463486	0.102	0.801	N	0.415	0.158	0.253205268125	gnomAD-4.0.0	1.3685E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79905E-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
K/A	0.3186	likely_benign	0.2856	benign	-0.15	Destabilizing	0.525	D	0.473	neutral	None	None	None	None	N
K/C	0.6233	likely_pathogenic	0.5673	pathogenic	-0.431	Destabilizing	0.998	D	0.535	neutral	None	None	None	None	N
K/D	0.5058	ambiguous	0.4591	ambiguous	0.273	Stabilizing	0.842	D	0.499	neutral	None	None	None	None	N
K/E	0.171	likely_benign	0.1512	benign	0.338	Stabilizing	0.625	D	0.409	neutral	N	0.475568679	None	None	N
K/F	0.7562	likely_pathogenic	0.6977	pathogenic	-0.119	Destabilizing	0.949	D	0.556	neutral	None	None	None	None	N
K/G	0.4468	ambiguous	0.3958	ambiguous	-0.419	Destabilizing	0.842	D	0.529	neutral	None	None	None	None	N
K/H	0.2837	likely_benign	0.2608	benign	-0.575	Destabilizing	0.974	D	0.5	neutral	None	None	None	None	N
K/I	0.3474	ambiguous	0.3035	benign	0.5	Stabilizing	0.904	D	0.553	neutral	None	None	None	None	N
K/L	0.3704	ambiguous	0.3245	benign	0.5	Stabilizing	0.525	D	0.545	neutral	None	None	None	None	N
K/M	0.217	likely_benign	0.1992	benign	0.107	Stabilizing	0.267	N	0.379	neutral	D	0.531270033	None	None	N
K/N	0.3185	likely_benign	0.2844	benign	-0.038	Destabilizing	0.801	D	0.415	neutral	N	0.425371932	None	None	N
K/P	0.6938	likely_pathogenic	0.6485	pathogenic	0.313	Stabilizing	0.991	D	0.506	neutral	None	None	None	None	N
K/Q	0.1359	likely_benign	0.1258	benign	-0.095	Destabilizing	0.801	D	0.487	neutral	N	0.45552148	None	None	N
K/R	0.0873	likely_benign	0.0875	benign	-0.132	Destabilizing	0.005	N	0.244	neutral	N	0.471587011	None	None	N
K/S	0.3387	likely_benign	0.2915	benign	-0.607	Destabilizing	0.172	N	0.249	neutral	None	None	None	None	N
K/T	0.1364	likely_benign	0.1225	benign	-0.358	Destabilizing	0.051	N	0.336	neutral	N	0.378658207	None	None	N
K/V	0.3153	likely_benign	0.2793	benign	0.313	Stabilizing	0.728	D	0.543	neutral	None	None	None	None	N
K/W	0.7045	likely_pathogenic	0.6599	pathogenic	-0.099	Destabilizing	0.998	D	0.555	neutral	None	None	None	None	N
K/Y	0.5635	ambiguous	0.5175	ambiguous	0.235	Stabilizing	0.991	D	0.549	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.