TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30195	90808;90809;90810	chr2:178552317;178552316;178552315	chr2:179417044;179417043;179417042
N2AB	28554	85885;85886;85887	chr2:178552317;178552316;178552315	chr2:179417044;179417043;179417042
N2A	27627	83104;83105;83106	chr2:178552317;178552316;178552315	chr2:179417044;179417043;179417042
N2B	21130	63613;63614;63615	chr2:178552317;178552316;178552315	chr2:179417044;179417043;179417042
Novex-1	21255	63988;63989;63990	chr2:178552317;178552316;178552315	chr2:179417044;179417043;179417042
Novex-2	21322	64189;64190;64191	chr2:178552317;178552316;178552315	chr2:179417044;179417043;179417042
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-148
• Domain position: 64
• Structural Position: 145
• Q(SASA): 0.6538
• 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/R	rs1699777024	None	0.001	N	0.237	0.067	0.329540904979	gnomAD-4.0.0	2.05684E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80063E-06	1.17148E-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	0.3438	ambiguous	0.3502	ambiguous	-0.725	Destabilizing	0.157	N	0.433	neutral	None	None	None	None	N
K/C	0.5941	likely_pathogenic	0.6021	pathogenic	-0.46	Destabilizing	0.968	D	0.699	prob.neutral	None	None	None	None	N
K/D	0.6247	likely_pathogenic	0.6012	pathogenic	-0.295	Destabilizing	0.567	D	0.409	neutral	None	None	None	None	N
K/E	0.1908	likely_benign	0.1893	benign	-0.153	Destabilizing	0.124	N	0.47	neutral	N	0.472259015	None	None	N
K/F	0.7769	likely_pathogenic	0.7785	pathogenic	-0.261	Destabilizing	0.726	D	0.643	neutral	None	None	None	None	N
K/G	0.3975	ambiguous	0.4074	ambiguous	-1.116	Destabilizing	0.272	N	0.445	neutral	None	None	None	None	N
K/H	0.3315	likely_benign	0.3342	benign	-1.388	Destabilizing	0.832	D	0.467	neutral	None	None	None	None	N
K/I	0.3998	ambiguous	0.3899	ambiguous	0.307	Stabilizing	0.726	D	0.645	neutral	None	None	None	None	N
K/L	0.3681	ambiguous	0.3722	ambiguous	0.307	Stabilizing	0.272	N	0.445	neutral	None	None	None	None	N
K/M	0.2805	likely_benign	0.2821	benign	0.124	Stabilizing	0.883	D	0.467	neutral	D	0.5327529	None	None	N
K/N	0.4552	ambiguous	0.4226	ambiguous	-0.556	Destabilizing	0.497	N	0.399	neutral	N	0.487999258	None	None	N
K/P	0.8606	likely_pathogenic	0.8425	pathogenic	-0.008	Destabilizing	0.726	D	0.453	neutral	None	None	None	None	N
K/Q	0.1103	likely_benign	0.1174	benign	-0.504	Destabilizing	0.002	N	0.277	neutral	N	0.442688256	None	None	N
K/R	0.074	likely_benign	0.0788	benign	-0.705	Destabilizing	0.001	N	0.237	neutral	N	0.44255497	None	None	N
K/S	0.3912	ambiguous	0.3953	ambiguous	-1.133	Destabilizing	0.157	N	0.432	neutral	None	None	None	None	N
K/T	0.193	likely_benign	0.1901	benign	-0.776	Destabilizing	0.497	N	0.411	neutral	N	0.457214991	None	None	N
K/V	0.3128	likely_benign	0.3244	benign	-0.008	Destabilizing	0.567	D	0.501	neutral	None	None	None	None	N
K/W	0.7669	likely_pathogenic	0.7709	pathogenic	-0.192	Destabilizing	0.968	D	0.702	prob.neutral	None	None	None	None	N
K/Y	0.6704	likely_pathogenic	0.6534	pathogenic	0.053	Stabilizing	0.726	D	0.589	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.