TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21854	65785;65786;65787	chr2:178583622;178583621;178583620	chr2:179448349;179448348;179448347
N2AB	20213	60862;60863;60864	chr2:178583622;178583621;178583620	chr2:179448349;179448348;179448347
N2A	19286	58081;58082;58083	chr2:178583622;178583621;178583620	chr2:179448349;179448348;179448347
N2B	12789	38590;38591;38592	chr2:178583622;178583621;178583620	chr2:179448349;179448348;179448347
Novex-1	12914	38965;38966;38967	chr2:178583622;178583621;178583620	chr2:179448349;179448348;179448347
Novex-2	12981	39166;39167;39168	chr2:178583622;178583621;178583620	chr2:179448349;179448348;179448347
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-46
• Domain position: 98
• Structural Position: 130
• Q(SASA): 0.028
• 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
I/L	None	None	0.098	N	0.311	0.038	0.307966526162	gnomAD-4.0.0	6.89351E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.05315E-07	0	0
I/V	None	None	0.001	N	0.115	0.032	0.215869574891	gnomAD-4.0.0	6.89351E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.05315E-07	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
I/A	0.6713	likely_pathogenic	0.6726	pathogenic	-2.833	Highly Destabilizing	0.248	N	0.641	neutral	None	None	None	None	N
I/C	0.8049	likely_pathogenic	0.8082	pathogenic	-2.478	Highly Destabilizing	0.977	D	0.661	prob.neutral	None	None	None	None	N
I/D	0.9936	likely_pathogenic	0.9945	pathogenic	-3.16	Highly Destabilizing	0.972	D	0.791	deleterious	None	None	None	None	N
I/E	0.9898	likely_pathogenic	0.9908	pathogenic	-2.95	Highly Destabilizing	0.919	D	0.734	deleterious	None	None	None	None	N
I/F	0.6979	likely_pathogenic	0.7075	pathogenic	-1.667	Destabilizing	0.808	D	0.698	prob.delet.	N	0.461107981	None	None	N
I/G	0.9628	likely_pathogenic	0.9644	pathogenic	-3.335	Highly Destabilizing	0.919	D	0.699	prob.delet.	None	None	None	None	N
I/H	0.9858	likely_pathogenic	0.9864	pathogenic	-2.545	Highly Destabilizing	0.992	D	0.781	deleterious	None	None	None	None	N
I/K	0.9836	likely_pathogenic	0.983	pathogenic	-2.127	Highly Destabilizing	0.919	D	0.736	deleterious	None	None	None	None	N
I/L	0.2648	likely_benign	0.2503	benign	-1.38	Destabilizing	0.098	N	0.311	neutral	N	0.475933172	None	None	N
I/M	0.4078	ambiguous	0.3924	ambiguous	-1.674	Destabilizing	0.808	D	0.676	prob.neutral	N	0.470068779	None	None	N
I/N	0.9055	likely_pathogenic	0.9186	pathogenic	-2.472	Highly Destabilizing	0.963	D	0.78	deleterious	N	0.460854491	None	None	N
I/P	0.832	likely_pathogenic	0.8215	pathogenic	-1.847	Destabilizing	0.972	D	0.795	deleterious	None	None	None	None	N
I/Q	0.9809	likely_pathogenic	0.9823	pathogenic	-2.386	Highly Destabilizing	0.972	D	0.785	deleterious	None	None	None	None	N
I/R	0.9654	likely_pathogenic	0.9681	pathogenic	-1.765	Destabilizing	0.919	D	0.776	deleterious	None	None	None	None	N
I/S	0.8529	likely_pathogenic	0.8677	pathogenic	-3.166	Highly Destabilizing	0.808	D	0.667	prob.neutral	N	0.460347512	None	None	N
I/T	0.7815	likely_pathogenic	0.7943	pathogenic	-2.817	Highly Destabilizing	0.546	D	0.677	prob.neutral	N	0.478880264	None	None	N
I/V	0.0655	likely_benign	0.0687	benign	-1.847	Destabilizing	0.001	N	0.115	neutral	N	0.386855537	None	None	N
I/W	0.994	likely_pathogenic	0.9939	pathogenic	-1.912	Destabilizing	0.992	D	0.778	deleterious	None	None	None	None	N
I/Y	0.9675	likely_pathogenic	0.9697	pathogenic	-1.721	Destabilizing	0.919	D	0.734	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.