TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4916	14971;14972;14973	chr2:178735700;178735699;178735698	chr2:179600427;179600426;179600425
N2AB	4599	14020;14021;14022	chr2:178735700;178735699;178735698	chr2:179600427;179600426;179600425
N2A	3672	11239;11240;11241	chr2:178735700;178735699;178735698	chr2:179600427;179600426;179600425
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-32
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.6661
• 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/E	rs376597173	0.2	0.959	N	0.337	0.225	None	gnomAD-2.1.1	7.14E-05	None	None	None	None	N	None	4.13E-05	8.49E-05	None	0	0	None	0	None	0	1.24957E-04	0
K/E	rs376597173	0.2	0.959	N	0.337	0.225	None	gnomAD-3.1.2	1.31403E-04	None	None	None	None	N	None	9.65E-05	0	0	0	0	None	0	0	2.20459E-04	0	4.78011E-04
K/E	rs376597173	0.2	0.959	N	0.337	0.225	None	gnomAD-4.0.0	1.1898E-04	None	None	None	None	N	None	6.67289E-05	8.33528E-05	None	0	0	None	0	0	1.47479E-04	0	1.28094E-04

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	0.2701	likely_benign	0.3367	benign	0.06	Stabilizing	0.079	N	0.192	neutral	None	None	None	None	N
K/C	0.7014	likely_pathogenic	0.7868	pathogenic	-0.284	Destabilizing	0.999	D	0.468	neutral	None	None	None	None	N
K/D	0.4117	ambiguous	0.5112	ambiguous	-0.088	Destabilizing	0.969	D	0.439	neutral	None	None	None	None	N
K/E	0.1399	likely_benign	0.1814	benign	-0.089	Destabilizing	0.959	D	0.337	neutral	N	0.489923653	None	None	N
K/F	0.7074	likely_pathogenic	0.7876	pathogenic	-0.198	Destabilizing	0.997	D	0.473	neutral	None	None	None	None	N
K/G	0.3618	ambiguous	0.4393	ambiguous	-0.109	Destabilizing	0.007	N	0.236	neutral	None	None	None	None	N
K/H	0.3073	likely_benign	0.3622	ambiguous	-0.311	Destabilizing	0.999	D	0.405	neutral	None	None	None	None	N
K/I	0.3434	ambiguous	0.4207	ambiguous	0.423	Stabilizing	0.988	D	0.479	neutral	N	0.515823936	None	None	N
K/L	0.2874	likely_benign	0.3385	benign	0.423	Stabilizing	0.939	D	0.447	neutral	None	None	None	None	N
K/M	0.1944	likely_benign	0.2297	benign	0.092	Stabilizing	0.999	D	0.401	neutral	None	None	None	None	N
K/N	0.2929	likely_benign	0.3588	ambiguous	0.143	Stabilizing	0.959	D	0.373	neutral	D	0.533807268	None	None	N
K/P	0.4959	ambiguous	0.5974	pathogenic	0.329	Stabilizing	0.991	D	0.413	neutral	None	None	None	None	N
K/Q	0.1366	likely_benign	0.1641	benign	-0.002	Destabilizing	0.996	D	0.405	neutral	N	0.498320661	None	None	N
K/R	0.0967	likely_benign	0.1052	benign	-0.082	Destabilizing	0.959	D	0.349	neutral	N	0.502320989	None	None	N
K/S	0.3448	ambiguous	0.4305	ambiguous	-0.264	Destabilizing	0.759	D	0.345	neutral	None	None	None	None	N
K/T	0.1625	likely_benign	0.2084	benign	-0.132	Destabilizing	0.92	D	0.393	neutral	N	0.484473168	None	None	N
K/V	0.3112	likely_benign	0.3904	ambiguous	0.329	Stabilizing	0.939	D	0.475	neutral	None	None	None	None	N
K/W	0.7399	likely_pathogenic	0.8092	pathogenic	-0.271	Destabilizing	0.999	D	0.519	neutral	None	None	None	None	N
K/Y	0.5731	likely_pathogenic	0.6556	pathogenic	0.085	Stabilizing	0.997	D	0.465	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.