TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30161	90706;90707;90708	chr2:178552419;178552418;178552417	chr2:179417146;179417145;179417144
N2AB	28520	85783;85784;85785	chr2:178552419;178552418;178552417	chr2:179417146;179417145;179417144
N2A	27593	83002;83003;83004	chr2:178552419;178552418;178552417	chr2:179417146;179417145;179417144
N2B	21096	63511;63512;63513	chr2:178552419;178552418;178552417	chr2:179417146;179417145;179417144
Novex-1	21221	63886;63887;63888	chr2:178552419;178552418;178552417	chr2:179417146;179417145;179417144
Novex-2	21288	64087;64088;64089	chr2:178552419;178552418;178552417	chr2:179417146;179417145;179417144
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-148
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.1305
• 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/S	None	None	1.0	D	0.84	0.677	0.627239104411	gnomAD-4.0.0	1.63395E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.47654E-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
P/A	0.4988	ambiguous	0.4517	ambiguous	-1.664	Destabilizing	1.0	D	0.778	deleterious	N	0.519914554	None	None	N
P/C	0.9647	likely_pathogenic	0.9519	pathogenic	-1.228	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
P/D	0.9977	likely_pathogenic	0.9975	pathogenic	-1.339	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
P/E	0.995	likely_pathogenic	0.9942	pathogenic	-1.303	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
P/F	0.9965	likely_pathogenic	0.9956	pathogenic	-1.328	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
P/G	0.9624	likely_pathogenic	0.9553	pathogenic	-2.03	Highly Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
P/H	0.993	likely_pathogenic	0.9922	pathogenic	-1.631	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
P/I	0.9262	likely_pathogenic	0.9189	pathogenic	-0.742	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
P/K	0.997	likely_pathogenic	0.9967	pathogenic	-1.26	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
P/L	0.8742	likely_pathogenic	0.8607	pathogenic	-0.742	Destabilizing	1.0	D	0.836	deleterious	D	0.532165778	None	None	N
P/M	0.9687	likely_pathogenic	0.9641	pathogenic	-0.604	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
P/N	0.9946	likely_pathogenic	0.9934	pathogenic	-1.098	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
P/Q	0.9889	likely_pathogenic	0.9866	pathogenic	-1.213	Destabilizing	1.0	D	0.85	deleterious	D	0.563226636	None	None	N
P/R	0.9922	likely_pathogenic	0.9919	pathogenic	-0.836	Destabilizing	1.0	D	0.843	deleterious	D	0.563226636	None	None	N
P/S	0.9476	likely_pathogenic	0.9341	pathogenic	-1.709	Destabilizing	1.0	D	0.84	deleterious	D	0.562719657	None	None	N
P/T	0.9011	likely_pathogenic	0.8867	pathogenic	-1.546	Destabilizing	1.0	D	0.847	deleterious	D	0.536221611	None	None	N
P/V	0.8241	likely_pathogenic	0.8169	pathogenic	-1.015	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
P/W	0.9993	likely_pathogenic	0.9991	pathogenic	-1.538	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
P/Y	0.9968	likely_pathogenic	0.9961	pathogenic	-1.227	Destabilizing	1.0	D	0.831	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.