TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28167	84724;84725;84726	chr2:178561633;178561632;178561631	chr2:179426360;179426359;179426358
N2AB	26526	79801;79802;79803	chr2:178561633;178561632;178561631	chr2:179426360;179426359;179426358
N2A	25599	77020;77021;77022	chr2:178561633;178561632;178561631	chr2:179426360;179426359;179426358
N2B	19102	57529;57530;57531	chr2:178561633;178561632;178561631	chr2:179426360;179426359;179426358
Novex-1	19227	57904;57905;57906	chr2:178561633;178561632;178561631	chr2:179426360;179426359;179426358
Novex-2	19294	58105;58106;58107	chr2:178561633;178561632;178561631	chr2:179426360;179426359;179426358
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-93
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.1979
• 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
T/I	rs1159274489	None	0.983	N	0.681	0.473	0.55911886355	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/I	rs1159274489	None	0.983	N	0.681	0.473	0.55911886355	gnomAD-4.0.0	6.57281E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46994E-05	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
T/A	0.1506	likely_benign	0.1398	benign	-0.59	Destabilizing	0.63	D	0.455	neutral	N	0.479071921	None	None	N
T/C	0.5841	likely_pathogenic	0.5462	ambiguous	-0.335	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	N
T/D	0.4791	ambiguous	0.451	ambiguous	-1.191	Destabilizing	0.975	D	0.634	neutral	None	None	None	None	N
T/E	0.6057	likely_pathogenic	0.5622	ambiguous	-1.175	Destabilizing	0.975	D	0.64	neutral	None	None	None	None	N
T/F	0.6343	likely_pathogenic	0.5806	pathogenic	-0.669	Destabilizing	0.987	D	0.706	prob.neutral	None	None	None	None	N
T/G	0.2047	likely_benign	0.1969	benign	-0.869	Destabilizing	0.845	D	0.551	neutral	None	None	None	None	N
T/H	0.4755	ambiguous	0.4396	ambiguous	-1.327	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	N
T/I	0.7266	likely_pathogenic	0.6853	pathogenic	0.07	Stabilizing	0.983	D	0.681	prob.neutral	N	0.496962367	None	None	N
T/K	0.4415	ambiguous	0.4082	ambiguous	-0.854	Destabilizing	0.967	D	0.641	neutral	N	0.486224718	None	None	N
T/L	0.2926	likely_benign	0.2544	benign	0.07	Stabilizing	0.916	D	0.578	neutral	None	None	None	None	N
T/M	0.21	likely_benign	0.1874	benign	0.529	Stabilizing	0.999	D	0.641	neutral	None	None	None	None	N
T/N	0.1409	likely_benign	0.1324	benign	-0.967	Destabilizing	0.975	D	0.627	neutral	None	None	None	None	N
T/P	0.7427	likely_pathogenic	0.7289	pathogenic	-0.117	Destabilizing	0.983	D	0.681	prob.neutral	N	0.519839562	None	None	N
T/Q	0.3839	ambiguous	0.3548	ambiguous	-1.139	Destabilizing	0.975	D	0.677	prob.neutral	None	None	None	None	N
T/R	0.3986	ambiguous	0.3531	ambiguous	-0.636	Destabilizing	0.967	D	0.686	prob.neutral	N	0.512481123	None	None	N
T/S	0.0912	likely_benign	0.0881	benign	-1.031	Destabilizing	0.099	N	0.23	neutral	N	0.434172268	None	None	N
T/V	0.4673	ambiguous	0.4264	ambiguous	-0.117	Destabilizing	0.916	D	0.537	neutral	None	None	None	None	N
T/W	0.8784	likely_pathogenic	0.8472	pathogenic	-0.739	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	N
T/Y	0.6278	likely_pathogenic	0.5823	pathogenic	-0.452	Destabilizing	0.996	D	0.709	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.