TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32216	96871;96872;96873	chr2:178543327;178543326;178543325	chr2:179408054;179408053;179408052
N2AB	30575	91948;91949;91950	chr2:178543327;178543326;178543325	chr2:179408054;179408053;179408052
N2A	29648	89167;89168;89169	chr2:178543327;178543326;178543325	chr2:179408054;179408053;179408052
N2B	23151	69676;69677;69678	chr2:178543327;178543326;178543325	chr2:179408054;179408053;179408052
Novex-1	23276	70051;70052;70053	chr2:178543327;178543326;178543325	chr2:179408054;179408053;179408052
Novex-2	23343	70252;70253;70254	chr2:178543327;178543326;178543325	chr2:179408054;179408053;179408052
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-123
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.491
• 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/Q	rs771585130	-0.453	0.978	N	0.688	0.293	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
K/Q	rs771585130	-0.453	0.978	N	0.688	0.293	None	gnomAD-4.0.0	4.77333E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71611E-06	0	3.02352E-05
K/T	rs1695519342	None	0.978	N	0.673	0.295	0.321393169273	gnomAD-4.0.0	2.05254E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	3.47794E-05	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	0.437	ambiguous	0.45	ambiguous	-0.19	Destabilizing	0.944	D	0.556	neutral	None	None	None	None	N
K/C	0.8268	likely_pathogenic	0.8354	pathogenic	-0.233	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
K/D	0.7919	likely_pathogenic	0.7964	pathogenic	-0.143	Destabilizing	0.983	D	0.719	prob.delet.	None	None	None	None	N
K/E	0.4076	ambiguous	0.4236	ambiguous	-0.141	Destabilizing	0.928	D	0.484	neutral	N	0.499295608	None	None	N
K/F	0.9508	likely_pathogenic	0.9503	pathogenic	-0.471	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
K/G	0.5117	ambiguous	0.5244	ambiguous	-0.41	Destabilizing	0.983	D	0.659	neutral	None	None	None	None	N
K/H	0.5152	ambiguous	0.4959	ambiguous	-0.875	Destabilizing	0.998	D	0.682	prob.neutral	None	None	None	None	N
K/I	0.8043	likely_pathogenic	0.8014	pathogenic	0.318	Stabilizing	0.989	D	0.776	deleterious	N	0.488093914	None	None	N
K/L	0.6824	likely_pathogenic	0.6751	pathogenic	0.318	Stabilizing	0.983	D	0.659	neutral	None	None	None	None	N
K/M	0.5737	likely_pathogenic	0.5865	pathogenic	0.431	Stabilizing	0.999	D	0.686	prob.neutral	None	None	None	None	N
K/N	0.6615	likely_pathogenic	0.6778	pathogenic	0.117	Stabilizing	0.978	D	0.689	prob.neutral	N	0.515939929	None	None	N
K/P	0.7283	likely_pathogenic	0.7373	pathogenic	0.178	Stabilizing	0.992	D	0.705	prob.neutral	None	None	None	None	N
K/Q	0.2297	likely_benign	0.2336	benign	-0.184	Destabilizing	0.978	D	0.688	prob.neutral	N	0.4721028	None	None	N
K/R	0.0807	likely_benign	0.0784	benign	-0.086	Destabilizing	0.085	N	0.28	neutral	N	0.454411467	None	None	N
K/S	0.5546	ambiguous	0.5593	ambiguous	-0.429	Destabilizing	0.944	D	0.595	neutral	None	None	None	None	N
K/T	0.4372	ambiguous	0.4341	ambiguous	-0.275	Destabilizing	0.978	D	0.673	neutral	N	0.467112369	None	None	N
K/V	0.6799	likely_pathogenic	0.6724	pathogenic	0.178	Stabilizing	0.983	D	0.723	prob.delet.	None	None	None	None	N
K/W	0.9335	likely_pathogenic	0.9309	pathogenic	-0.399	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
K/Y	0.8617	likely_pathogenic	0.8633	pathogenic	-0.029	Destabilizing	0.997	D	0.76	deleterious	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.