TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13998	42217;42218;42219	chr2:178635197;178635196;178635195	chr2:179499924;179499923;179499922
N2AB	12357	37294;37295;37296	chr2:178635197;178635196;178635195	chr2:179499924;179499923;179499922
N2A	11430	34513;34514;34515	chr2:178635197;178635196;178635195	chr2:179499924;179499923;179499922
N2B	4933	15022;15023;15024	chr2:178635197;178635196;178635195	chr2:179499924;179499923;179499922
Novex-1	5058	15397;15398;15399	chr2:178635197;178635196;178635195	chr2:179499924;179499923;179499922
Novex-2	5125	15598;15599;15600	chr2:178635197;178635196;178635195	chr2:179499924;179499923;179499922
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-90
• Domain position: 34
• Structural Position: 49
• Q(SASA): 0.2464
• 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/N	None	None	0.999	N	0.735	0.279	0.141422826196	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0
K/Q	None	None	0.999	N	0.696	0.285	0.171388866994	gnomAD-4.0.0	1.5931E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86084E-06	0	0
K/T	None	None	0.999	N	0.784	0.489	0.227260227426	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.8912	likely_pathogenic	0.7702	pathogenic	-0.962	Destabilizing	0.998	D	0.735	deleterious	None	None	None	None	N
K/C	0.9182	likely_pathogenic	0.8596	pathogenic	-1.075	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
K/D	0.9851	likely_pathogenic	0.9612	pathogenic	-0.525	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
K/E	0.838	likely_pathogenic	0.6123	pathogenic	-0.326	Destabilizing	0.997	D	0.683	prob.neutral	N	0.412083635	None	None	N
K/F	0.8599	likely_pathogenic	0.8011	pathogenic	-0.346	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
K/G	0.9455	likely_pathogenic	0.883	pathogenic	-1.4	Destabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
K/H	0.5459	ambiguous	0.4389	ambiguous	-1.558	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
K/I	0.6903	likely_pathogenic	0.5098	ambiguous	0.224	Stabilizing	0.999	D	0.885	deleterious	N	0.422968619	None	None	N
K/L	0.5857	likely_pathogenic	0.4704	ambiguous	0.224	Stabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
K/M	0.4173	ambiguous	0.2807	benign	-0.052	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
K/N	0.9146	likely_pathogenic	0.7983	pathogenic	-0.971	Destabilizing	0.999	D	0.735	deleterious	N	0.478477397	None	None	N
K/P	0.9989	likely_pathogenic	0.9977	pathogenic	-0.144	Destabilizing	0.999	D	0.818	deleterious	None	None	None	None	N
K/Q	0.3889	ambiguous	0.2279	benign	-0.885	Destabilizing	0.999	D	0.696	prob.delet.	N	0.412632833	None	None	N
K/R	0.1581	likely_benign	0.1229	benign	-0.803	Destabilizing	0.997	D	0.655	prob.neutral	N	0.476134984	None	None	N
K/S	0.9178	likely_pathogenic	0.7997	pathogenic	-1.684	Destabilizing	0.998	D	0.695	prob.delet.	None	None	None	None	N
K/T	0.7022	likely_pathogenic	0.4639	ambiguous	-1.247	Destabilizing	0.999	D	0.784	deleterious	N	0.431925063	None	None	N
K/V	0.6807	likely_pathogenic	0.5271	ambiguous	-0.144	Destabilizing	0.999	D	0.834	deleterious	None	None	None	None	N
K/W	0.9162	likely_pathogenic	0.8626	pathogenic	-0.225	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
K/Y	0.6728	likely_pathogenic	0.6085	pathogenic	0.082	Stabilizing	1.0	D	0.877	deleterious	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.