TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8649	26170;26171;26172	chr2:178715241;178715240;178715239	chr2:179579968;179579967;179579966
N2AB	8332	25219;25220;25221	chr2:178715241;178715240;178715239	chr2:179579968;179579967;179579966
N2A	7405	22438;22439;22440	chr2:178715241;178715240;178715239	chr2:179579968;179579967;179579966
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-72
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.2824
• Predicted PPI site: I

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	rs1414275142	-0.411	0.999	N	0.675	0.393	0.532359089423	gnomAD-2.1.1	4.14E-06	None	None	None	None	I	None	0	0	None	1.04493E-04	0	None	0	None	0	0	0
P/L	rs1414275142	-0.411	0.999	N	0.675	0.393	0.532359089423	gnomAD-4.0.0	1.61329E-06	None	None	None	None	I	None	0	0	None	4.84966E-05	0	None	0	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
P/A	0.2528	likely_benign	0.2905	benign	-1.757	Destabilizing	0.288	N	0.329	neutral	N	0.503235655	None	None	I
P/C	0.8001	likely_pathogenic	0.8365	pathogenic	-0.785	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
P/D	0.9548	likely_pathogenic	0.9695	pathogenic	-1.945	Destabilizing	0.986	D	0.657	neutral	None	None	None	None	I
P/E	0.891	likely_pathogenic	0.9268	pathogenic	-1.917	Destabilizing	0.982	D	0.63	neutral	None	None	None	None	I
P/F	0.7866	likely_pathogenic	0.8255	pathogenic	-1.285	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
P/G	0.7674	likely_pathogenic	0.8246	pathogenic	-2.102	Highly Destabilizing	0.99	D	0.595	neutral	None	None	None	None	I
P/H	0.7623	likely_pathogenic	0.8241	pathogenic	-1.871	Destabilizing	1.0	D	0.665	neutral	D	0.531001148	None	None	I
P/I	0.4255	ambiguous	0.456	ambiguous	-0.871	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
P/K	0.917	likely_pathogenic	0.9439	pathogenic	-1.552	Destabilizing	0.996	D	0.612	neutral	None	None	None	None	I
P/L	0.1822	likely_benign	0.2058	benign	-0.871	Destabilizing	0.999	D	0.675	prob.neutral	N	0.469972779	None	None	I
P/M	0.4698	ambiguous	0.509	ambiguous	-0.456	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	I
P/N	0.8652	likely_pathogenic	0.902	pathogenic	-1.248	Destabilizing	0.998	D	0.684	prob.neutral	None	None	None	None	I
P/Q	0.7189	likely_pathogenic	0.792	pathogenic	-1.383	Destabilizing	0.998	D	0.669	neutral	None	None	None	None	I
P/R	0.8304	likely_pathogenic	0.8776	pathogenic	-1.06	Destabilizing	0.729	D	0.398	neutral	D	0.530494169	None	None	I
P/S	0.588	likely_pathogenic	0.6694	pathogenic	-1.68	Destabilizing	0.981	D	0.613	neutral	N	0.503742634	None	None	I
P/T	0.3657	ambiguous	0.4229	ambiguous	-1.562	Destabilizing	0.994	D	0.634	neutral	N	0.512136425	None	None	I
P/V	0.3675	ambiguous	0.3911	ambiguous	-1.137	Destabilizing	0.997	D	0.632	neutral	None	None	None	None	I
P/W	0.931	likely_pathogenic	0.9517	pathogenic	-1.609	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	I
P/Y	0.8514	likely_pathogenic	0.893	pathogenic	-1.353	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I

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.