TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14167	42724;42725;42726	chr2:178634000;178633999;178633998	chr2:179498727;179498726;179498725
N2AB	12526	37801;37802;37803	chr2:178634000;178633999;178633998	chr2:179498727;179498726;179498725
N2A	11599	35020;35021;35022	chr2:178634000;178633999;178633998	chr2:179498727;179498726;179498725
N2B	5102	15529;15530;15531	chr2:178634000;178633999;178633998	chr2:179498727;179498726;179498725
Novex-1	5227	15904;15905;15906	chr2:178634000;178633999;178633998	chr2:179498727;179498726;179498725
Novex-2	5294	16105;16106;16107	chr2:178634000;178633999;178633998	chr2:179498727;179498726;179498725
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-92
• Domain position: 26
• Structural Position: 40
• Q(SASA): 0.5689
• 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
H/R	None	None	0.997	N	0.449	0.492	0.362758974969	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25001E-06	0	0
H/Y	None	None	0.999	D	0.46	0.489	0.606237419447	gnomAD-4.0.0	1.59221E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88274E-05	0	0	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
H/A	0.7316	likely_pathogenic	0.6433	pathogenic	0.208	Stabilizing	0.993	D	0.459	neutral	None	None	None	None	N
H/C	0.5845	likely_pathogenic	0.512	ambiguous	0.743	Stabilizing	1.0	D	0.627	neutral	None	None	None	None	N
H/D	0.6152	likely_pathogenic	0.4948	ambiguous	-0.19	Destabilizing	0.135	N	0.261	neutral	N	0.505416429	None	None	N
H/E	0.6937	likely_pathogenic	0.5865	pathogenic	-0.134	Destabilizing	0.971	D	0.415	neutral	None	None	None	None	N
H/F	0.6424	likely_pathogenic	0.6296	pathogenic	1.153	Stabilizing	0.999	D	0.461	neutral	None	None	None	None	N
H/G	0.7658	likely_pathogenic	0.6996	pathogenic	-0.116	Destabilizing	0.993	D	0.461	neutral	None	None	None	None	N
H/I	0.8142	likely_pathogenic	0.7469	pathogenic	1.059	Stabilizing	0.999	D	0.614	neutral	None	None	None	None	N
H/K	0.6023	likely_pathogenic	0.5718	pathogenic	0.211	Stabilizing	0.993	D	0.382	neutral	None	None	None	None	N
H/L	0.4103	ambiguous	0.3478	ambiguous	1.059	Stabilizing	0.999	D	0.555	neutral	D	0.553085668	None	None	N
H/M	0.8492	likely_pathogenic	0.8102	pathogenic	0.746	Stabilizing	1.0	D	0.561	neutral	None	None	None	None	N
H/N	0.3339	likely_benign	0.2584	benign	0.111	Stabilizing	0.98	D	0.453	neutral	N	0.496835219	None	None	N
H/P	0.6022	likely_pathogenic	0.5304	ambiguous	0.8	Stabilizing	0.999	D	0.551	neutral	N	0.505400675	None	None	N
H/Q	0.5747	likely_pathogenic	0.4741	ambiguous	0.276	Stabilizing	0.997	D	0.458	neutral	D	0.535853725	None	None	N
H/R	0.3429	ambiguous	0.2925	benign	-0.485	Destabilizing	0.997	D	0.449	neutral	N	0.508588814	None	None	N
H/S	0.6125	likely_pathogenic	0.529	ambiguous	0.26	Stabilizing	0.985	D	0.423	neutral	None	None	None	None	N
H/T	0.7641	likely_pathogenic	0.6815	pathogenic	0.422	Stabilizing	0.998	D	0.468	neutral	None	None	None	None	N
H/V	0.7244	likely_pathogenic	0.6474	pathogenic	0.8	Stabilizing	0.999	D	0.593	neutral	None	None	None	None	N
H/W	0.6847	likely_pathogenic	0.6794	pathogenic	1.222	Stabilizing	1.0	D	0.605	neutral	None	None	None	None	N
H/Y	0.2665	likely_benign	0.2567	benign	1.41	Stabilizing	0.999	D	0.46	neutral	D	0.61850101	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.