TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15658	47197;47198;47199	chr2:178618486;178618485;178618484	chr2:179483213;179483212;179483211
N2AB	14017	42274;42275;42276	chr2:178618486;178618485;178618484	chr2:179483213;179483212;179483211
N2A	13090	39493;39494;39495	chr2:178618486;178618485;178618484	chr2:179483213;179483212;179483211
N2B	6593	20002;20003;20004	chr2:178618486;178618485;178618484	chr2:179483213;179483212;179483211
Novex-1	6718	20377;20378;20379	chr2:178618486;178618485;178618484	chr2:179483213;179483212;179483211
Novex-2	6785	20578;20579;20580	chr2:178618486;178618485;178618484	chr2:179483213;179483212;179483211
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-1
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.1192
• 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
P/L	rs794729440	None	1.0	D	0.799	0.77	0.765417107005	gnomAD-4.0.0	1.5971E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86518E-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
P/A	0.9023	likely_pathogenic	0.908	pathogenic	-1.422	Destabilizing	0.999	D	0.791	deleterious	D	0.719474093	None	None	N
P/C	0.9952	likely_pathogenic	0.9944	pathogenic	-2.125	Highly Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
P/D	0.9994	likely_pathogenic	0.9991	pathogenic	-3.042	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
P/E	0.9984	likely_pathogenic	0.9976	pathogenic	-2.987	Highly Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
P/F	0.9998	likely_pathogenic	0.9998	pathogenic	-1.167	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
P/G	0.994	likely_pathogenic	0.9926	pathogenic	-1.715	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
P/H	0.9989	likely_pathogenic	0.9985	pathogenic	-1.132	Destabilizing	1.0	D	0.775	deleterious	D	0.786976731	None	None	N
P/I	0.9966	likely_pathogenic	0.9959	pathogenic	-0.684	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
P/K	0.9993	likely_pathogenic	0.999	pathogenic	-1.391	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
P/L	0.986	likely_pathogenic	0.9854	pathogenic	-0.684	Destabilizing	1.0	D	0.799	deleterious	D	0.787519374	None	None	N
P/M	0.9985	likely_pathogenic	0.9984	pathogenic	-1.071	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
P/N	0.9994	likely_pathogenic	0.9992	pathogenic	-1.696	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
P/Q	0.9982	likely_pathogenic	0.9977	pathogenic	-1.892	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
P/R	0.9964	likely_pathogenic	0.9951	pathogenic	-0.936	Destabilizing	1.0	D	0.803	deleterious	D	0.787519374	None	None	N
P/S	0.9913	likely_pathogenic	0.9901	pathogenic	-2.042	Highly Destabilizing	1.0	D	0.786	deleterious	D	0.733599032	None	None	N
P/T	0.9898	likely_pathogenic	0.9872	pathogenic	-1.885	Destabilizing	1.0	D	0.796	deleterious	D	0.787519374	None	None	N
P/V	0.9863	likely_pathogenic	0.9842	pathogenic	-0.903	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
P/W	0.9999	likely_pathogenic	0.9999	pathogenic	-1.427	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
P/Y	0.9998	likely_pathogenic	0.9997	pathogenic	-1.053	Destabilizing	1.0	D	0.837	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.