TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30665	92218;92219;92220	chr2:178549729;178549728;178549727	chr2:179414456;179414455;179414454
N2AB	29024	87295;87296;87297	chr2:178549729;178549728;178549727	chr2:179414456;179414455;179414454
N2A	28097	84514;84515;84516	chr2:178549729;178549728;178549727	chr2:179414456;179414455;179414454
N2B	21600	65023;65024;65025	chr2:178549729;178549728;178549727	chr2:179414456;179414455;179414454
Novex-1	21725	65398;65399;65400	chr2:178549729;178549728;178549727	chr2:179414456;179414455;179414454
Novex-2	21792	65599;65600;65601	chr2:178549729;178549728;178549727	chr2:179414456;179414455;179414454
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-111
• Domain position: 47
• Structural Position: 63
• Q(SASA): 1.0994
• Predicted PPI site: I

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
L/P	rs1412840625	None	0.995	N	0.553	0.557	0.818544703288	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/P	rs1412840625	None	0.995	N	0.553	0.557	0.818544703288	gnomAD-4.0.0	6.57177E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.46981E-05	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
L/A	0.6554	likely_pathogenic	0.6671	pathogenic	-0.447	Destabilizing	0.702	D	0.469	neutral	None	None	None	None	I
L/C	0.8989	likely_pathogenic	0.91	pathogenic	-0.857	Destabilizing	0.999	D	0.567	neutral	None	None	None	None	I
L/D	0.9638	likely_pathogenic	0.9612	pathogenic	-0.155	Destabilizing	0.996	D	0.545	neutral	None	None	None	None	I
L/E	0.8477	likely_pathogenic	0.8367	pathogenic	-0.241	Destabilizing	0.988	D	0.543	neutral	None	None	None	None	I
L/F	0.5043	ambiguous	0.5683	pathogenic	-0.607	Destabilizing	0.968	D	0.487	neutral	N	0.499107825	None	None	I
L/G	0.8928	likely_pathogenic	0.9009	pathogenic	-0.534	Destabilizing	0.988	D	0.531	neutral	None	None	None	None	I
L/H	0.7658	likely_pathogenic	0.7858	pathogenic	0.097	Stabilizing	0.999	D	0.561	neutral	N	0.492106386	None	None	I
L/I	0.1591	likely_benign	0.1701	benign	-0.334	Destabilizing	0.011	N	0.155	neutral	N	0.475559067	None	None	I
L/K	0.7379	likely_pathogenic	0.7137	pathogenic	-0.347	Destabilizing	0.988	D	0.519	neutral	None	None	None	None	I
L/M	0.235	likely_benign	0.2413	benign	-0.655	Destabilizing	0.976	D	0.499	neutral	None	None	None	None	I
L/N	0.8226	likely_pathogenic	0.8057	pathogenic	-0.235	Destabilizing	0.996	D	0.556	neutral	None	None	None	None	I
L/P	0.6581	likely_pathogenic	0.6896	pathogenic	-0.346	Destabilizing	0.995	D	0.553	neutral	N	0.521788466	None	None	I
L/Q	0.6041	likely_pathogenic	0.6032	pathogenic	-0.388	Destabilizing	0.996	D	0.55	neutral	None	None	None	None	I
L/R	0.6641	likely_pathogenic	0.6632	pathogenic	0.076	Stabilizing	0.984	D	0.545	neutral	N	0.509456674	None	None	I
L/S	0.8213	likely_pathogenic	0.8308	pathogenic	-0.629	Destabilizing	0.988	D	0.479	neutral	None	None	None	None	I
L/T	0.6629	likely_pathogenic	0.6432	pathogenic	-0.618	Destabilizing	0.919	D	0.469	neutral	None	None	None	None	I
L/V	0.1811	likely_benign	0.2013	benign	-0.346	Destabilizing	0.011	N	0.161	neutral	N	0.494833938	None	None	I
L/W	0.7392	likely_pathogenic	0.7749	pathogenic	-0.622	Destabilizing	0.999	D	0.605	neutral	None	None	None	None	I
L/Y	0.7978	likely_pathogenic	0.8143	pathogenic	-0.401	Destabilizing	0.988	D	0.517	neutral	None	None	None	None	I

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.