TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9174	27745;27746;27747	chr2:178712402;178712401;178712400	chr2:179577129;179577128;179577127
N2AB	8857	26794;26795;26796	chr2:178712402;178712401;178712400	chr2:179577129;179577128;179577127
N2A	7930	24013;24014;24015	chr2:178712402;178712401;178712400	chr2:179577129;179577128;179577127
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: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-77
• Domain position: 63
• Structural Position: 144
• Q(SASA): 0.0942
• 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/N	None	None	None	N	0.209	0.197	0.207176502487	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	0.0944	likely_benign	0.0862	benign	-0.707	Destabilizing	0.007	N	0.361	neutral	None	None	None	None	N
S/C	0.1031	likely_benign	0.0977	benign	-1.048	Destabilizing	None	N	0.412	neutral	N	0.470162859	None	None	N
S/D	0.8466	likely_pathogenic	0.8122	pathogenic	-1.791	Destabilizing	0.038	N	0.465	neutral	None	None	None	None	N
S/E	0.9345	likely_pathogenic	0.9154	pathogenic	-1.71	Destabilizing	0.072	N	0.491	neutral	None	None	None	None	N
S/F	0.6662	likely_pathogenic	0.5746	pathogenic	-1.05	Destabilizing	0.12	N	0.647	neutral	None	None	None	None	N
S/G	0.122	likely_benign	0.117	benign	-0.955	Destabilizing	None	N	0.209	neutral	N	0.48875743	None	None	N
S/H	0.8298	likely_pathogenic	0.7897	pathogenic	-1.422	Destabilizing	0.214	N	0.599	neutral	None	None	None	None	N
S/I	0.2865	likely_benign	0.2524	benign	-0.137	Destabilizing	0.001	N	0.449	neutral	N	0.481008997	None	None	N
S/K	0.9817	likely_pathogenic	0.9724	pathogenic	-0.588	Destabilizing	0.072	N	0.491	neutral	None	None	None	None	N
S/L	0.227	likely_benign	0.1747	benign	-0.137	Destabilizing	0.016	N	0.503	neutral	None	None	None	None	N
S/M	0.4402	ambiguous	0.3618	ambiguous	-0.034	Destabilizing	0.356	N	0.6	neutral	None	None	None	None	N
S/N	0.3011	likely_benign	0.2771	benign	-1.093	Destabilizing	None	N	0.209	neutral	N	0.515255476	None	None	N
S/P	0.5842	likely_pathogenic	0.4537	ambiguous	-0.297	Destabilizing	0.356	N	0.637	neutral	None	None	None	None	N
S/Q	0.9187	likely_pathogenic	0.8929	pathogenic	-1.222	Destabilizing	0.356	N	0.601	neutral	None	None	None	None	N
S/R	0.9587	likely_pathogenic	0.9447	pathogenic	-0.553	Destabilizing	0.055	N	0.629	neutral	N	0.515255476	None	None	N
S/T	0.1137	likely_benign	0.0938	benign	-0.831	Destabilizing	None	N	0.226	neutral	N	0.471162936	None	None	N
S/V	0.2596	likely_benign	0.2174	benign	-0.297	Destabilizing	0.016	N	0.509	neutral	None	None	None	None	N
S/W	0.8583	likely_pathogenic	0.806	pathogenic	-1.198	Destabilizing	0.864	D	0.589	neutral	None	None	None	None	N
S/Y	0.6619	likely_pathogenic	0.579	pathogenic	-0.771	Destabilizing	0.001	N	0.447	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.