TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13712	41359;41360;41361	chr2:178636593;178636592;178636591	chr2:179501320;179501319;179501318
N2AB	12071	36436;36437;36438	chr2:178636593;178636592;178636591	chr2:179501320;179501319;179501318
N2A	11144	33655;33656;33657	chr2:178636593;178636592;178636591	chr2:179501320;179501319;179501318
N2B	4647	14164;14165;14166	chr2:178636593;178636592;178636591	chr2:179501320;179501319;179501318
Novex-1	4772	14539;14540;14541	chr2:178636593;178636592;178636591	chr2:179501320;179501319;179501318
Novex-2	4839	14740;14741;14742	chr2:178636593;178636592;178636591	chr2:179501320;179501319;179501318
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-87
• Domain position: 29
• Structural Position: 40
• Q(SASA): 0.2747
• 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	rs1425096489	-0.237	0.993	D	0.741	0.393	0.75374075986	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
P/L	rs1425096489	-0.237	0.993	D	0.741	0.393	0.75374075986	gnomAD-4.0.0	1.36869E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79921E-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	0.9778	likely_pathogenic	0.9856	pathogenic	-0.661	Destabilizing	0.977	D	0.655	neutral	N	0.501504195	None	None	N
P/C	0.9993	likely_pathogenic	0.9995	pathogenic	-0.675	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
P/D	0.9985	likely_pathogenic	0.999	pathogenic	-0.039	Destabilizing	0.998	D	0.763	deleterious	None	None	None	None	N
P/E	0.9975	likely_pathogenic	0.9979	pathogenic	-0.118	Destabilizing	0.995	D	0.753	deleterious	None	None	None	None	N
P/F	0.9997	likely_pathogenic	0.9997	pathogenic	-0.658	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
P/G	0.9906	likely_pathogenic	0.9932	pathogenic	-0.849	Destabilizing	0.998	D	0.727	prob.delet.	None	None	None	None	N
P/H	0.9967	likely_pathogenic	0.9969	pathogenic	-0.266	Destabilizing	0.999	D	0.693	prob.neutral	N	0.506009482	None	None	N
P/I	0.9988	likely_pathogenic	0.9991	pathogenic	-0.298	Destabilizing	0.998	D	0.731	prob.delet.	None	None	None	None	N
P/K	0.9979	likely_pathogenic	0.9982	pathogenic	-0.475	Destabilizing	0.966	D	0.707	prob.neutral	None	None	None	None	N
P/L	0.993	likely_pathogenic	0.9945	pathogenic	-0.298	Destabilizing	0.993	D	0.741	deleterious	D	0.527261277	None	None	N
P/M	0.999	likely_pathogenic	0.9992	pathogenic	-0.354	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
P/N	0.9975	likely_pathogenic	0.9981	pathogenic	-0.224	Destabilizing	0.995	D	0.698	prob.neutral	None	None	None	None	N
P/Q	0.9958	likely_pathogenic	0.9969	pathogenic	-0.417	Destabilizing	0.995	D	0.731	prob.delet.	None	None	None	None	N
P/R	0.994	likely_pathogenic	0.9943	pathogenic	0.021	Stabilizing	0.235	N	0.423	neutral	N	0.497615493	None	None	N
P/S	0.99	likely_pathogenic	0.9939	pathogenic	-0.715	Destabilizing	0.993	D	0.746	deleterious	N	0.500608132	None	None	N
P/T	0.9881	likely_pathogenic	0.9936	pathogenic	-0.679	Destabilizing	0.997	D	0.757	deleterious	N	0.505600606	None	None	N
P/V	0.9948	likely_pathogenic	0.9962	pathogenic	-0.382	Destabilizing	0.998	D	0.727	prob.delet.	None	None	None	None	N
P/W	0.9999	likely_pathogenic	0.9999	pathogenic	-0.726	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
P/Y	0.9995	likely_pathogenic	0.9995	pathogenic	-0.438	Destabilizing	1.0	D	0.737	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.