TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21336	64231;64232;64233	chr2:178587205;178587204;178587203	chr2:179451932;179451931;179451930
N2AB	19695	59308;59309;59310	chr2:178587205;178587204;178587203	chr2:179451932;179451931;179451930
N2A	18768	56527;56528;56529	chr2:178587205;178587204;178587203	chr2:179451932;179451931;179451930
N2B	12271	37036;37037;37038	chr2:178587205;178587204;178587203	chr2:179451932;179451931;179451930
Novex-1	12396	37411;37412;37413	chr2:178587205;178587204;178587203	chr2:179451932;179451931;179451930
Novex-2	12463	37612;37613;37614	chr2:178587205;178587204;178587203	chr2:179451932;179451931;179451930
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-42
• Domain position: 71
• Structural Position: 104
• Q(SASA): 0.0777
• 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
Y/C	None	None	1.0	D	0.867	0.911	0.876811852075	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
Y/A	0.9915	likely_pathogenic	0.9875	pathogenic	-3.413	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
Y/C	0.9147	likely_pathogenic	0.873	pathogenic	-1.896	Destabilizing	1.0	D	0.867	deleterious	D	0.6761862	None	None	N
Y/D	0.99	likely_pathogenic	0.9871	pathogenic	-3.537	Highly Destabilizing	1.0	D	0.873	deleterious	D	0.6761862	None	None	N
Y/E	0.998	likely_pathogenic	0.997	pathogenic	-3.341	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
Y/F	0.2577	likely_benign	0.2198	benign	-1.289	Destabilizing	0.999	D	0.749	deleterious	D	0.620972091	None	None	N
Y/G	0.9774	likely_pathogenic	0.9716	pathogenic	-3.816	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
Y/H	0.9584	likely_pathogenic	0.9337	pathogenic	-2.26	Highly Destabilizing	1.0	D	0.818	deleterious	D	0.6761862	None	None	N
Y/I	0.9552	likely_pathogenic	0.9341	pathogenic	-2.063	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
Y/K	0.9983	likely_pathogenic	0.9969	pathogenic	-2.314	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
Y/L	0.9515	likely_pathogenic	0.9368	pathogenic	-2.063	Highly Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
Y/M	0.9732	likely_pathogenic	0.9596	pathogenic	-1.735	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
Y/N	0.9165	likely_pathogenic	0.8794	pathogenic	-3.031	Highly Destabilizing	1.0	D	0.866	deleterious	D	0.675984395	None	None	N
Y/P	0.9991	likely_pathogenic	0.9985	pathogenic	-2.529	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
Y/Q	0.9964	likely_pathogenic	0.9936	pathogenic	-2.83	Highly Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
Y/R	0.9956	likely_pathogenic	0.9923	pathogenic	-1.946	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
Y/S	0.972	likely_pathogenic	0.9599	pathogenic	-3.412	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.6761862	None	None	N
Y/T	0.9876	likely_pathogenic	0.9803	pathogenic	-3.104	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
Y/V	0.931	likely_pathogenic	0.9032	pathogenic	-2.529	Highly Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
Y/W	0.8574	likely_pathogenic	0.8341	pathogenic	-0.553	Destabilizing	1.0	D	0.801	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.