TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22895	68908;68909;68910	chr2:178577743;178577742;178577741	chr2:179442470;179442469;179442468
N2AB	21254	63985;63986;63987	chr2:178577743;178577742;178577741	chr2:179442470;179442469;179442468
N2A	20327	61204;61205;61206	chr2:178577743;178577742;178577741	chr2:179442470;179442469;179442468
N2B	13830	41713;41714;41715	chr2:178577743;178577742;178577741	chr2:179442470;179442469;179442468
Novex-1	13955	42088;42089;42090	chr2:178577743;178577742;178577741	chr2:179442470;179442469;179442468
Novex-2	14022	42289;42290;42291	chr2:178577743;178577742;178577741	chr2:179442470;179442469;179442468
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-54
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.359
• 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
N/D	rs2046758201	None	0.958	N	0.399	0.397	0.315609569513	gnomAD-4.0.0	1.5921E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43345E-05	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
N/A	0.3078	likely_benign	0.3449	ambiguous	-0.394	Destabilizing	0.938	D	0.539	neutral	None	None	None	None	N
N/C	0.4082	ambiguous	0.4535	ambiguous	0.291	Stabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
N/D	0.3439	ambiguous	0.3989	ambiguous	0.061	Stabilizing	0.958	D	0.399	neutral	N	0.489564191	None	None	N
N/E	0.7343	likely_pathogenic	0.7969	pathogenic	0.023	Stabilizing	0.938	D	0.431	neutral	None	None	None	None	N
N/F	0.6249	likely_pathogenic	0.6801	pathogenic	-0.786	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
N/G	0.494	ambiguous	0.5225	ambiguous	-0.561	Destabilizing	0.968	D	0.41	neutral	None	None	None	None	N
N/H	0.2037	likely_benign	0.2432	benign	-0.621	Destabilizing	0.994	D	0.637	neutral	N	0.476296763	None	None	N
N/I	0.2149	likely_benign	0.2438	benign	-0.042	Destabilizing	0.994	D	0.759	deleterious	N	0.469357776	None	None	N
N/K	0.7401	likely_pathogenic	0.8033	pathogenic	0.107	Stabilizing	0.067	N	0.304	neutral	D	0.523868766	None	None	N
N/L	0.2305	likely_benign	0.2588	benign	-0.042	Destabilizing	0.991	D	0.689	prob.neutral	None	None	None	None	N
N/M	0.327	likely_benign	0.3596	ambiguous	0.348	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
N/P	0.4586	ambiguous	0.539	ambiguous	-0.133	Destabilizing	0.995	D	0.71	prob.delet.	None	None	None	None	N
N/Q	0.6061	likely_pathogenic	0.6708	pathogenic	-0.427	Destabilizing	0.991	D	0.65	neutral	None	None	None	None	N
N/R	0.7331	likely_pathogenic	0.8026	pathogenic	0.155	Stabilizing	0.982	D	0.549	neutral	None	None	None	None	N
N/S	0.1101	likely_benign	0.1127	benign	-0.171	Destabilizing	0.958	D	0.375	neutral	N	0.46492355	None	None	N
N/T	0.1658	likely_benign	0.1755	benign	-0.064	Destabilizing	0.958	D	0.466	neutral	N	0.506165652	None	None	N
N/V	0.2363	likely_benign	0.2666	benign	-0.133	Destabilizing	0.991	D	0.745	deleterious	None	None	None	None	N
N/W	0.8615	likely_pathogenic	0.897	pathogenic	-0.753	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
N/Y	0.251	likely_benign	0.3052	benign	-0.487	Destabilizing	0.998	D	0.717	prob.delet.	N	0.497630249	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.