TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32564	97915;97916;97917	chr2:178541387;178541386;178541385	chr2:179406114;179406113;179406112
N2AB	30923	92992;92993;92994	chr2:178541387;178541386;178541385	chr2:179406114;179406113;179406112
N2A	29996	90211;90212;90213	chr2:178541387;178541386;178541385	chr2:179406114;179406113;179406112
N2B	23499	70720;70721;70722	chr2:178541387;178541386;178541385	chr2:179406114;179406113;179406112
Novex-1	23624	71095;71096;71097	chr2:178541387;178541386;178541385	chr2:179406114;179406113;179406112
Novex-2	23691	71296;71297;71298	chr2:178541387;178541386;178541385	chr2:179406114;179406113;179406112
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-125
• Domain position: 66
• Structural Position: 97
• Q(SASA): 0.1169
• 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
L/R	None	None	0.989	D	0.877	0.905	0.939919551497	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
L/A	0.9636	likely_pathogenic	0.9715	pathogenic	-2.329	Highly Destabilizing	0.895	D	0.824	deleterious	None	None	None	None	N
L/C	0.9126	likely_pathogenic	0.9208	pathogenic	-2.013	Highly Destabilizing	0.999	D	0.832	deleterious	None	None	None	None	N
L/D	0.9982	likely_pathogenic	0.9987	pathogenic	-2.283	Highly Destabilizing	0.997	D	0.886	deleterious	None	None	None	None	N
L/E	0.9912	likely_pathogenic	0.994	pathogenic	-2.206	Highly Destabilizing	0.992	D	0.882	deleterious	None	None	None	None	N
L/F	0.7582	likely_pathogenic	0.7903	pathogenic	-1.786	Destabilizing	0.978	D	0.885	deleterious	D	0.638509471	None	None	N
L/G	0.9893	likely_pathogenic	0.9913	pathogenic	-2.727	Highly Destabilizing	0.992	D	0.887	deleterious	None	None	None	None	N
L/H	0.9777	likely_pathogenic	0.9839	pathogenic	-1.892	Destabilizing	0.999	D	0.861	deleterious	D	0.6648548	None	None	N
L/I	0.3088	likely_benign	0.3919	ambiguous	-1.245	Destabilizing	0.688	D	0.835	deleterious	D	0.621248924	None	None	N
L/K	0.9798	likely_pathogenic	0.9839	pathogenic	-1.619	Destabilizing	0.992	D	0.878	deleterious	None	None	None	None	N
L/M	0.4363	ambiguous	0.4529	ambiguous	-1.159	Destabilizing	0.983	D	0.859	deleterious	None	None	None	None	N
L/N	0.983	likely_pathogenic	0.9863	pathogenic	-1.678	Destabilizing	0.997	D	0.881	deleterious	None	None	None	None	N
L/P	0.9902	likely_pathogenic	0.9937	pathogenic	-1.582	Destabilizing	0.996	D	0.888	deleterious	D	0.6648548	None	None	N
L/Q	0.9585	likely_pathogenic	0.9688	pathogenic	-1.826	Destabilizing	0.997	D	0.873	deleterious	None	None	None	None	N
L/R	0.9651	likely_pathogenic	0.975	pathogenic	-1.04	Destabilizing	0.989	D	0.877	deleterious	D	0.648603274	None	None	N
L/S	0.9905	likely_pathogenic	0.9935	pathogenic	-2.399	Highly Destabilizing	0.983	D	0.871	deleterious	None	None	None	None	N
L/T	0.9656	likely_pathogenic	0.9757	pathogenic	-2.192	Highly Destabilizing	0.983	D	0.86	deleterious	None	None	None	None	N
L/V	0.4475	ambiguous	0.5372	ambiguous	-1.582	Destabilizing	0.039	N	0.607	neutral	D	0.573765894	None	None	N
L/W	0.9602	likely_pathogenic	0.9699	pathogenic	-1.902	Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
L/Y	0.9666	likely_pathogenic	0.9698	pathogenic	-1.662	Destabilizing	0.992	D	0.849	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.