TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6996	21211;21212;21213	chr2:178724389;178724388;178724387	chr2:179589116;179589115;179589114
N2AB	6679	20260;20261;20262	chr2:178724389;178724388;178724387	chr2:179589116;179589115;179589114
N2A	5752	17479;17480;17481	chr2:178724389;178724388;178724387	chr2:179589116;179589115;179589114
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: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-54
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.2691
• 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
F/C	rs2078977093	None	0.975	N	0.535	0.441	0.807077759815	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
F/L	rs753725329	-0.75	0.065	N	0.166	0.154	0.199424873507	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	1.78E-05	0
F/L	rs753725329	-0.75	0.065	N	0.166	0.154	0.199424873507	gnomAD-4.0.0	3.18377E-06	None	None	None	None	N	None	0	2.28739E-05	None	0	0	None	0	0	2.85946E-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
F/A	0.531	ambiguous	0.5748	pathogenic	-2.218	Highly Destabilizing	0.3	N	0.311	neutral	None	None	None	None	N
F/C	0.2844	likely_benign	0.3077	benign	-1.474	Destabilizing	0.975	D	0.535	neutral	N	0.4854922	None	None	N
F/D	0.7914	likely_pathogenic	0.842	pathogenic	-0.868	Destabilizing	0.936	D	0.623	neutral	None	None	None	None	N
F/E	0.7686	likely_pathogenic	0.8193	pathogenic	-0.714	Destabilizing	0.936	D	0.584	neutral	None	None	None	None	N
F/G	0.7758	likely_pathogenic	0.8019	pathogenic	-2.61	Highly Destabilizing	0.936	D	0.529	neutral	None	None	None	None	N
F/H	0.601	likely_pathogenic	0.6213	pathogenic	-0.926	Destabilizing	0.981	D	0.517	neutral	None	None	None	None	N
F/I	0.0721	likely_benign	0.0837	benign	-1.007	Destabilizing	0.001	N	0.065	neutral	N	0.375460399	None	None	N
F/K	0.7431	likely_pathogenic	0.8017	pathogenic	-1.364	Destabilizing	0.828	D	0.583	neutral	None	None	None	None	N
F/L	0.6642	likely_pathogenic	0.6681	pathogenic	-1.007	Destabilizing	0.065	N	0.166	neutral	N	0.419867324	None	None	N
F/M	0.3011	likely_benign	0.3468	ambiguous	-0.862	Destabilizing	0.893	D	0.468	neutral	None	None	None	None	N
F/N	0.5727	likely_pathogenic	0.6262	pathogenic	-1.546	Destabilizing	0.981	D	0.597	neutral	None	None	None	None	N
F/P	0.93	likely_pathogenic	0.9349	pathogenic	-1.409	Destabilizing	0.981	D	0.602	neutral	None	None	None	None	N
F/Q	0.675	likely_pathogenic	0.7319	pathogenic	-1.491	Destabilizing	0.981	D	0.547	neutral	None	None	None	None	N
F/R	0.6502	likely_pathogenic	0.705	pathogenic	-0.889	Destabilizing	0.981	D	0.58	neutral	None	None	None	None	N
F/S	0.4527	ambiguous	0.4924	ambiguous	-2.446	Highly Destabilizing	0.784	D	0.495	neutral	N	0.468624064	None	None	N
F/T	0.4534	ambiguous	0.496	ambiguous	-2.185	Highly Destabilizing	0.495	N	0.393	neutral	None	None	None	None	N
F/V	0.1176	likely_benign	0.1272	benign	-1.409	Destabilizing	0.003	N	0.185	neutral	N	0.411898415	None	None	N
F/W	0.4788	ambiguous	0.4906	ambiguous	-0.117	Destabilizing	0.995	D	0.46	neutral	None	None	None	None	N
F/Y	0.1291	likely_benign	0.1283	benign	-0.411	Destabilizing	0.917	D	0.38	neutral	N	0.460100581	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.