TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34315	103168;103169;103170	chr2:178533672;178533671;178533670	chr2:179398399;179398398;179398397
N2AB	32674	98245;98246;98247	chr2:178533672;178533671;178533670	chr2:179398399;179398398;179398397
N2A	31747	95464;95465;95466	chr2:178533672;178533671;178533670	chr2:179398399;179398398;179398397
N2B	25250	75973;75974;75975	chr2:178533672;178533671;178533670	chr2:179398399;179398398;179398397
Novex-1	25375	76348;76349;76350	chr2:178533672;178533671;178533670	chr2:179398399;179398398;179398397
Novex-2	25442	76549;76550;76551	chr2:178533672;178533671;178533670	chr2:179398399;179398398;179398397
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-161
• Domain position: 58
• Structural Position: 135
• Q(SASA): 0.5
• 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/I	rs1305429779	None	0.955	N	0.521	0.279	0.503621591648	gnomAD-4.0.0	1.59103E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85767E-06	0	0
L/V	rs1305429779	None	0.955	N	0.566	0.294	0.507687591559	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
L/V	rs1305429779	None	0.955	N	0.566	0.294	0.507687591559	gnomAD-4.0.0	1.59103E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02371E-05

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	0.8393	likely_pathogenic	0.7601	pathogenic	-1.572	Destabilizing	0.983	D	0.675	neutral	None	None	None	None	N
L/C	0.8421	likely_pathogenic	0.8126	pathogenic	-0.96	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
L/D	0.9665	likely_pathogenic	0.9494	pathogenic	-0.808	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
L/E	0.8753	likely_pathogenic	0.8046	pathogenic	-0.815	Destabilizing	0.998	D	0.775	deleterious	None	None	None	None	N
L/F	0.4346	ambiguous	0.3758	ambiguous	-1.155	Destabilizing	0.993	D	0.779	deleterious	N	0.500139049	None	None	N
L/G	0.9349	likely_pathogenic	0.9146	pathogenic	-1.88	Destabilizing	0.998	D	0.768	deleterious	None	None	None	None	N
L/H	0.6793	likely_pathogenic	0.6009	pathogenic	-1.086	Destabilizing	1.0	D	0.751	deleterious	D	0.527728295	None	None	N
L/I	0.2329	likely_benign	0.1951	benign	-0.811	Destabilizing	0.955	D	0.521	neutral	N	0.478030194	None	None	N
L/K	0.693	likely_pathogenic	0.6058	pathogenic	-0.867	Destabilizing	0.995	D	0.769	deleterious	None	None	None	None	N
L/M	0.3115	likely_benign	0.2619	benign	-0.634	Destabilizing	0.921	D	0.471	neutral	None	None	None	None	N
L/N	0.826	likely_pathogenic	0.7488	pathogenic	-0.644	Destabilizing	0.999	D	0.786	deleterious	None	None	None	None	N
L/P	0.978	likely_pathogenic	0.977	pathogenic	-1.033	Destabilizing	0.999	D	0.788	deleterious	N	0.488922014	None	None	N
L/Q	0.5896	likely_pathogenic	0.469	ambiguous	-0.852	Destabilizing	0.998	D	0.779	deleterious	None	None	None	None	N
L/R	0.5071	ambiguous	0.4264	ambiguous	-0.321	Destabilizing	0.997	D	0.777	deleterious	N	0.432508548	None	None	N
L/S	0.8793	likely_pathogenic	0.8125	pathogenic	-1.309	Destabilizing	0.998	D	0.761	deleterious	None	None	None	None	N
L/T	0.769	likely_pathogenic	0.6749	pathogenic	-1.201	Destabilizing	0.995	D	0.756	deleterious	None	None	None	None	N
L/V	0.3299	likely_benign	0.2725	benign	-1.033	Destabilizing	0.955	D	0.566	neutral	N	0.458329712	None	None	N
L/W	0.6724	likely_pathogenic	0.6406	pathogenic	-1.176	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
L/Y	0.738	likely_pathogenic	0.652	pathogenic	-0.943	Destabilizing	0.998	D	0.795	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.