TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17535	52828;52829;52830	chr2:178608280;178608279;178608278	chr2:179473007;179473006;179473005
N2AB	15894	47905;47906;47907	chr2:178608280;178608279;178608278	chr2:179473007;179473006;179473005
N2A	14967	45124;45125;45126	chr2:178608280;178608279;178608278	chr2:179473007;179473006;179473005
N2B	8470	25633;25634;25635	chr2:178608280;178608279;178608278	chr2:179473007;179473006;179473005
Novex-1	8595	26008;26009;26010	chr2:178608280;178608279;178608278	chr2:179473007;179473006;179473005
Novex-2	8662	26209;26210;26211	chr2:178608280;178608279;178608278	chr2:179473007;179473006;179473005
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Fn3-15
• Domain position: 66
• Structural Position: 98
• Q(SASA): 0.6432
• 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/V	None	None	0.992	N	0.403	0.23	0.346315397577	gnomAD-4.0.0	1.59531E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88658E-05	0	0	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	0.5507	ambiguous	0.4363	ambiguous	-1.16	Destabilizing	0.997	D	0.591	neutral	None	None	None	None	N
L/C	0.7896	likely_pathogenic	0.7209	pathogenic	-0.896	Destabilizing	1.0	D	0.658	neutral	None	None	None	None	N
L/D	0.9331	likely_pathogenic	0.8883	pathogenic	-0.047	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
L/E	0.7258	likely_pathogenic	0.6105	pathogenic	-0.044	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
L/F	0.3866	ambiguous	0.3253	benign	-0.709	Destabilizing	0.999	D	0.675	neutral	N	0.492623139	None	None	N
L/G	0.8512	likely_pathogenic	0.7867	pathogenic	-1.443	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
L/H	0.5661	likely_pathogenic	0.4516	ambiguous	-0.433	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
L/I	0.1696	likely_benign	0.147	benign	-0.479	Destabilizing	0.992	D	0.403	neutral	N	0.402675925	None	None	N
L/K	0.6065	likely_pathogenic	0.4831	ambiguous	-0.592	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
L/M	0.1836	likely_benign	0.1482	benign	-0.575	Destabilizing	0.985	D	0.351	neutral	None	None	None	None	N
L/N	0.757	likely_pathogenic	0.655	pathogenic	-0.514	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
L/P	0.8283	likely_pathogenic	0.7673	pathogenic	-0.673	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
L/Q	0.357	ambiguous	0.2613	benign	-0.614	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
L/R	0.4886	ambiguous	0.4066	ambiguous	-0.086	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
L/S	0.6724	likely_pathogenic	0.5455	ambiguous	-1.186	Destabilizing	0.999	D	0.672	neutral	N	0.44490655	None	None	N
L/T	0.4659	ambiguous	0.3267	benign	-1.052	Destabilizing	1.0	D	0.66	neutral	None	None	None	None	N
L/V	0.1841	likely_benign	0.1475	benign	-0.673	Destabilizing	0.992	D	0.403	neutral	N	0.429457095	None	None	N
L/W	0.5362	ambiguous	0.468	ambiguous	-0.714	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
L/Y	0.6751	likely_pathogenic	0.6054	pathogenic	-0.49	Destabilizing	1.0	D	0.716	prob.delet.	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.