TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24652	74179;74180;74181	chr2:178572178;178572177;178572176	chr2:179436905;179436904;179436903
N2AB	23011	69256;69257;69258	chr2:178572178;178572177;178572176	chr2:179436905;179436904;179436903
N2A	22084	66475;66476;66477	chr2:178572178;178572177;178572176	chr2:179436905;179436904;179436903
N2B	15587	46984;46985;46986	chr2:178572178;178572177;178572176	chr2:179436905;179436904;179436903
Novex-1	15712	47359;47360;47361	chr2:178572178;178572177;178572176	chr2:179436905;179436904;179436903
Novex-2	15779	47560;47561;47562	chr2:178572178;178572177;178572176	chr2:179436905;179436904;179436903
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-67
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.2046
• 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
I/F	rs760045336	-1.563	0.988	N	0.548	0.332	0.622623412334	gnomAD-2.1.1	6.37E-05	None	None	None	None	N	None	2.2941E-04	0	None	0	0	None	0	None	0	0	0
I/F	rs760045336	-1.563	0.988	N	0.548	0.332	0.622623412334	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
I/F	rs760045336	-1.563	0.988	N	0.548	0.332	0.622623412334	gnomAD-4.0.0	5.12675E-06	None	None	None	None	N	None	3.38318E-05	0	None	0	0	None	0	0	4.7878E-06	0	0
I/L	None	None	0.266	N	0.438	0.122	0.583365392187	gnomAD-4.0.0	1.5921E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85938E-06	0	0
I/N	None	None	0.286	N	0.585	0.278	0.663445045466	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07039E-04	0
I/N	None	None	0.286	N	0.585	0.278	0.663445045466	gnomAD-4.0.0	6.57454E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.07039E-04	0
I/S	rs377752584	-2.305	0.968	N	0.6	0.303	0.739879714019	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
I/S	rs377752584	-2.305	0.968	N	0.6	0.303	0.739879714019	gnomAD-4.0.0	1.36872E-06	None	None	None	None	N	None	0	2.23694E-05	None	0	0	None	0	0	8.99582E-07	0	0
I/T	rs377752584	-2.036	0.9	N	0.544	0.333	None	gnomAD-2.1.1	6.37E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.29634E-04	0
I/T	rs377752584	-2.036	0.9	N	0.544	0.333	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	4.41E-05	0	0
I/T	rs377752584	-2.036	0.9	N	0.544	0.333	None	gnomAD-4.0.0	4.95871E-06	None	None	None	None	N	None	1.33511E-05	0	None	3.37883E-05	2.23494E-05	None	0	0	4.23865E-06	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
I/A	0.2651	likely_benign	0.2615	benign	-2.161	Highly Destabilizing	0.975	D	0.527	neutral	None	None	None	None	N
I/C	0.6062	likely_pathogenic	0.6252	pathogenic	-1.622	Destabilizing	1.0	D	0.632	neutral	None	None	None	None	N
I/D	0.7729	likely_pathogenic	0.7836	pathogenic	-1.931	Destabilizing	0.986	D	0.673	neutral	None	None	None	None	N
I/E	0.5841	likely_pathogenic	0.6134	pathogenic	-1.852	Destabilizing	0.967	D	0.676	prob.neutral	None	None	None	None	N
I/F	0.1809	likely_benign	0.1814	benign	-1.436	Destabilizing	0.988	D	0.548	neutral	N	0.512246263	None	None	N
I/G	0.7135	likely_pathogenic	0.7167	pathogenic	-2.562	Highly Destabilizing	0.975	D	0.637	neutral	None	None	None	None	N
I/H	0.3498	ambiguous	0.381	ambiguous	-1.73	Destabilizing	0.107	N	0.573	neutral	None	None	None	None	N
I/K	0.2713	likely_benign	0.2927	benign	-1.505	Destabilizing	0.804	D	0.677	prob.neutral	None	None	None	None	N
I/L	0.1106	likely_benign	0.1151	benign	-1.078	Destabilizing	0.266	N	0.438	neutral	N	0.481749997	None	None	N
I/M	0.1013	likely_benign	0.1009	benign	-1.015	Destabilizing	0.987	D	0.566	neutral	N	0.466102092	None	None	N
I/N	0.2673	likely_benign	0.2874	benign	-1.502	Destabilizing	0.286	N	0.585	neutral	N	0.507531089	None	None	N
I/P	0.9802	likely_pathogenic	0.9778	pathogenic	-1.412	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
I/Q	0.3506	ambiguous	0.3853	ambiguous	-1.622	Destabilizing	0.983	D	0.715	prob.delet.	None	None	None	None	N
I/R	0.2001	likely_benign	0.2167	benign	-0.963	Destabilizing	0.982	D	0.709	prob.delet.	None	None	None	None	N
I/S	0.2592	likely_benign	0.2747	benign	-2.203	Highly Destabilizing	0.968	D	0.6	neutral	N	0.520401599	None	None	N
I/T	0.1146	likely_benign	0.1142	benign	-2.0	Highly Destabilizing	0.9	D	0.544	neutral	N	0.484096869	None	None	N
I/V	0.0655	likely_benign	0.0645	benign	-1.412	Destabilizing	0.492	N	0.441	neutral	N	0.436575068	None	None	N
I/W	0.7539	likely_pathogenic	0.7389	pathogenic	-1.565	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
I/Y	0.4614	ambiguous	0.4786	ambiguous	-1.329	Destabilizing	0.765	D	0.619	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.