TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16012	48259;48260;48261	chr2:178616855;178616854;178616853	chr2:179481582;179481581;179481580
N2AB	14371	43336;43337;43338	chr2:178616855;178616854;178616853	chr2:179481582;179481581;179481580
N2A	13444	40555;40556;40557	chr2:178616855;178616854;178616853	chr2:179481582;179481581;179481580
N2B	6947	21064;21065;21066	chr2:178616855;178616854;178616853	chr2:179481582;179481581;179481580
Novex-1	7072	21439;21440;21441	chr2:178616855;178616854;178616853	chr2:179481582;179481581;179481580
Novex-2	7139	21640;21641;21642	chr2:178616855;178616854;178616853	chr2:179481582;179481581;179481580
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-109
• Domain position: 45
• Structural Position: 125
• Q(SASA): 0.4993
• 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/T	rs2057430031	None	0.023	N	0.174	0.192	0.26169431596	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07125E-04	0
K/T	rs2057430031	None	0.023	N	0.174	0.192	0.26169431596	gnomAD-4.0.0	6.58215E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.07125E-04	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	0.2969	likely_benign	0.3534	ambiguous	-0.5	Destabilizing	0.495	N	0.313	neutral	None	None	None	None	N
K/C	0.6335	likely_pathogenic	0.6836	pathogenic	-0.635	Destabilizing	0.995	D	0.327	neutral	None	None	None	None	N
K/D	0.3655	ambiguous	0.4286	ambiguous	-0.168	Destabilizing	0.543	D	0.399	neutral	None	None	None	None	N
K/E	0.1369	likely_benign	0.1666	benign	-0.052	Destabilizing	0.006	N	0.091	neutral	N	0.480442911	None	None	N
K/F	0.743	likely_pathogenic	0.7754	pathogenic	-0.208	Destabilizing	0.893	D	0.39	neutral	None	None	None	None	N
K/G	0.4359	ambiguous	0.4791	ambiguous	-0.847	Destabilizing	0.704	D	0.425	neutral	None	None	None	None	N
K/H	0.2338	likely_benign	0.2577	benign	-1.041	Destabilizing	0.944	D	0.354	neutral	None	None	None	None	N
K/I	0.3044	likely_benign	0.3647	ambiguous	0.393	Stabilizing	0.543	D	0.453	neutral	None	None	None	None	N
K/L	0.3515	ambiguous	0.405	ambiguous	0.393	Stabilizing	0.329	N	0.332	neutral	None	None	None	None	N
K/M	0.2218	likely_benign	0.2647	benign	0.047	Stabilizing	0.065	N	0.18	neutral	D	0.565344046	None	None	N
K/N	0.2069	likely_benign	0.2534	benign	-0.527	Destabilizing	0.642	D	0.308	neutral	D	0.562855301	None	None	N
K/P	0.897	likely_pathogenic	0.9019	pathogenic	0.125	Stabilizing	0.828	D	0.401	neutral	None	None	None	None	N
K/Q	0.1153	likely_benign	0.1306	benign	-0.52	Destabilizing	0.023	N	0.189	neutral	N	0.48735299	None	None	N
K/R	0.0886	likely_benign	0.0905	benign	-0.531	Destabilizing	0.473	N	0.301	neutral	N	0.511021556	None	None	N
K/S	0.2938	likely_benign	0.3443	ambiguous	-1.096	Destabilizing	0.329	N	0.282	neutral	None	None	None	None	N
K/T	0.1266	likely_benign	0.1581	benign	-0.775	Destabilizing	0.023	N	0.174	neutral	N	0.49683401	None	None	N
K/V	0.256	likely_benign	0.3134	benign	0.125	Stabilizing	0.013	N	0.137	neutral	None	None	None	None	N
K/W	0.7867	likely_pathogenic	0.7986	pathogenic	-0.147	Destabilizing	0.995	D	0.334	neutral	None	None	None	None	N
K/Y	0.5944	likely_pathogenic	0.6326	pathogenic	0.14	Stabilizing	0.981	D	0.37	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.