TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34997	105214;105215;105216	chr2:178531626;178531625;178531624	chr2:179396353;179396352;179396351
N2AB	33356	100291;100292;100293	chr2:178531626;178531625;178531624	chr2:179396353;179396352;179396351
N2A	32429	97510;97511;97512	chr2:178531626;178531625;178531624	chr2:179396353;179396352;179396351
N2B	25932	78019;78020;78021	chr2:178531626;178531625;178531624	chr2:179396353;179396352;179396351
Novex-1	26057	78394;78395;78396	chr2:178531626;178531625;178531624	chr2:179396353;179396352;179396351
Novex-2	26124	78595;78596;78597	chr2:178531626;178531625;178531624	chr2:179396353;179396352;179396351
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-163
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.1082
• 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
L/V	rs771364302	-1.498	0.117	N	0.502	0.041	0.271763555656	gnomAD-2.1.1	7.13E-05	None	None	None	None	N	None	0	0	None	0	1.02448E-03	None	0	None	0	0	0
L/V	rs771364302	-1.498	0.117	N	0.502	0.041	0.271763555656	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92604E-04	None	0	0	0	0	0
L/V	rs771364302	-1.498	0.117	N	0.502	0.041	0.271763555656	gnomAD-4.0.0	1.17729E-05	None	None	None	None	N	None	0	0	None	0	4.23238E-04	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
L/A	0.7487	likely_pathogenic	0.8783	pathogenic	-2.441	Highly Destabilizing	0.966	D	0.661	neutral	None	None	None	None	N
L/C	0.8158	likely_pathogenic	0.9239	pathogenic	-2.181	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
L/D	0.9893	likely_pathogenic	0.9964	pathogenic	-2.986	Highly Destabilizing	0.999	D	0.903	deleterious	None	None	None	None	N
L/E	0.9397	likely_pathogenic	0.9781	pathogenic	-2.783	Highly Destabilizing	0.998	D	0.891	deleterious	None	None	None	None	N
L/F	0.5215	ambiguous	0.8177	pathogenic	-1.524	Destabilizing	0.997	D	0.839	deleterious	N	0.477506466	None	None	N
L/G	0.962	likely_pathogenic	0.9826	pathogenic	-2.972	Highly Destabilizing	0.998	D	0.881	deleterious	None	None	None	None	N
L/H	0.8062	likely_pathogenic	0.9475	pathogenic	-2.491	Highly Destabilizing	1.0	D	0.896	deleterious	N	0.444009968	None	None	N
L/I	0.1963	likely_benign	0.3707	ambiguous	-0.909	Destabilizing	0.955	D	0.652	neutral	N	0.491937201	None	None	N
L/K	0.8893	likely_pathogenic	0.9657	pathogenic	-1.822	Destabilizing	0.998	D	0.866	deleterious	None	None	None	None	N
L/M	0.2364	likely_benign	0.3851	ambiguous	-1.049	Destabilizing	0.998	D	0.851	deleterious	None	None	None	None	N
L/N	0.9239	likely_pathogenic	0.9736	pathogenic	-2.189	Highly Destabilizing	0.999	D	0.902	deleterious	None	None	None	None	N
L/P	0.9946	likely_pathogenic	0.9979	pathogenic	-1.4	Destabilizing	0.999	D	0.903	deleterious	N	0.456199093	None	None	N
L/Q	0.7129	likely_pathogenic	0.8976	pathogenic	-2.082	Highly Destabilizing	0.999	D	0.908	deleterious	None	None	None	None	N
L/R	0.8189	likely_pathogenic	0.9433	pathogenic	-1.543	Destabilizing	0.999	D	0.91	deleterious	N	0.491763842	None	None	N
L/S	0.8593	likely_pathogenic	0.9583	pathogenic	-2.878	Highly Destabilizing	0.998	D	0.869	deleterious	None	None	None	None	N
L/T	0.6872	likely_pathogenic	0.8783	pathogenic	-2.526	Highly Destabilizing	0.995	D	0.794	deleterious	None	None	None	None	N
L/V	0.2069	likely_benign	0.4024	ambiguous	-1.4	Destabilizing	0.117	N	0.502	neutral	N	0.452648094	None	None	N
L/W	0.8253	likely_pathogenic	0.9619	pathogenic	-1.93	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
L/Y	0.8378	likely_pathogenic	0.9575	pathogenic	-1.654	Destabilizing	0.999	D	0.886	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.