TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4892	14899;14900;14901	chr2:178735772;178735771;178735770	chr2:179600499;179600498;179600497
N2AB	4575	13948;13949;13950	chr2:178735772;178735771;178735770	chr2:179600499;179600498;179600497
N2A	3648	11167;11168;11169	chr2:178735772;178735771;178735770	chr2:179600499;179600498;179600497
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: 5
• Structural Position: 5
• Q(SASA): 0.7145
• 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	rs1200349655	0.125	0.999	N	0.615	0.407	0.422524665647	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
K/E	rs1200349655	0.125	0.999	N	0.615	0.407	0.422524665647	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/E	rs1200349655	0.125	0.999	N	0.615	0.407	0.422524665647	gnomAD-4.0.0	1.30139E-05	None	None	None	None	N	None	1.33422E-05	0	None	0	0	None	0	0	1.61043E-05	0	1.60149E-05

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	0.5897	likely_pathogenic	0.5168	ambiguous	-0.453	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	N
K/C	0.8175	likely_pathogenic	0.7687	pathogenic	-0.442	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
K/D	0.7998	likely_pathogenic	0.7575	pathogenic	-0.167	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	N
K/E	0.2595	likely_benign	0.2133	benign	-0.05	Destabilizing	0.999	D	0.615	neutral	N	0.509764227	None	None	N
K/F	0.9042	likely_pathogenic	0.8712	pathogenic	0.02	Stabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
K/G	0.6536	likely_pathogenic	0.6061	pathogenic	-0.829	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	N
K/H	0.4583	ambiguous	0.3895	ambiguous	-1.091	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	N
K/I	0.6134	likely_pathogenic	0.5341	ambiguous	0.525	Stabilizing	1.0	D	0.72	prob.delet.	D	0.52995995	None	None	N
K/L	0.5526	ambiguous	0.4867	ambiguous	0.525	Stabilizing	1.0	D	0.647	neutral	None	None	None	None	N
K/M	0.3965	ambiguous	0.344	ambiguous	0.266	Stabilizing	1.0	D	0.649	neutral	None	None	None	None	N
K/N	0.6605	likely_pathogenic	0.5973	pathogenic	-0.466	Destabilizing	1.0	D	0.693	prob.neutral	N	0.511636613	None	None	N
K/P	0.9259	likely_pathogenic	0.9437	pathogenic	0.229	Stabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
K/Q	0.1969	likely_benign	0.1638	benign	-0.478	Destabilizing	1.0	D	0.685	prob.neutral	N	0.500910637	None	None	N
K/R	0.0911	likely_benign	0.0882	benign	-0.642	Destabilizing	0.999	D	0.548	neutral	N	0.502849283	None	None	N
K/S	0.6326	likely_pathogenic	0.5666	pathogenic	-1.033	Destabilizing	0.999	D	0.622	neutral	None	None	None	None	N
K/T	0.3128	likely_benign	0.2689	benign	-0.717	Destabilizing	1.0	D	0.682	prob.neutral	N	0.502918738	None	None	N
K/V	0.5625	ambiguous	0.4779	ambiguous	0.229	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
K/W	0.8329	likely_pathogenic	0.7905	pathogenic	0.099	Stabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
K/Y	0.7947	likely_pathogenic	0.7463	pathogenic	0.352	Stabilizing	1.0	D	0.667	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.