TABLE 1.
This table summarizes all reported homozygous mutations in TMC1 with origin information as well as clinical details and impaired domain positions of TMC1
| Nucleotide position (cDNA) | Predicted effect | Type of variant | Exon (E) /Intron (I) | Onset of HL | Severity of HL | Domain | Origin and Ref. |
|---|---|---|---|---|---|---|---|
| ‐258A>C | – | Regulatory | E3 | – | Severe to profound | – | Iran (Davoudi‐Dehaghani et al., 2013) |
| ‐259C>T | – | Regulatory | E3 | – | Severe to profound | – | Iran (Hilgert et al., 2009) |
| 16+1G>T | Splice disruption | Splicing | I5 | Prelingual | Severe to profound | – | Pakistan (Kitajiri et al., 2007) |
| 64+2T>A | Splice disruption | Splicing | I6 | Congenital/Prelingual | Profound | – | Turkey (Nakanishi et al., 2014) |
| 100C>T | p.R34X | Nonsense | E7 | Prelingual | Severe to profound | N‐terminus | Pakistan (Kitajiri et al., 2007; Kurima et al., 2002) |
| 150delT | p.N50KfsX26 | Frameshift | E7 | Congenital | Profound | N‐terminus | Iran (Yang et al., 2010) |
| ‐195_16del | 27 Kb deletion | Deletion | E5 | Prelingual | Severe to profound | – | Pakistan (Kurima et al., 2002) |
| 236+1G>A | p.E83X | Nonsense | I7 | Congenital | Severe to profound | – | Iran (Hilgert et al., 2008) |
| 237‐6T>G | Splice disruption | Splicing | I7 | Prelingual | Severe to profound | – | India (El Maghraoui, 2011) |
| 256G>T | p.Glu86X | Nonsense | E8 | Prelingual | Profound | N‐terminus | Iran (Sadeghian et al., 2019) |
| 295delA | p.K99KfsX4 | Frameshift | E8 | Prelingual | Severe to profound | N‐terminus | North America (Indian) (Kurima et al., 2002) |
| 362+18A>G | p.Glu122Tyrfs*10 | Frameshift | I8 | Congenital | Severe to profound | – | Pakistan (Shafique et al., 2014) |
| 362+3A>G | Splice disruption | Splicing | E8 | Prelingual | Severe to profound | – | Saudi (Ramzan et al., 2020) |
| 453+2T>C | Splice disruption | Splicing | ‐ | Prelingual | Severe to profound | – | India (Ganapathy et al., 2014) |
| 530T>C | p.(lle177Thr) | Missense | E10 | Prelingual | Profound | – | Iran (present study) |
| 536‐8T>A | Splice disruption | Splicing | I10 | Prelingual | Severe to profound | – | Pakistan (Kurima et al., 2002) |
| 536‐8T>A | Splice disruption | Splicing | I10 | Prelingual | Severe to profound | – | Pakistan (Santos et al., 2005) |
| c.758C > T | p.Ser253Phe | Missense | E8 | Prelingual | Severe | – | Saudi (Ramzan et al., 2020) |
| 767delT | p.F255FfsX14 | Frameshift | E13 | Congenital | Severe to profound | T1‐T2 | Turkey (Hilgert et al., 2008) |
| 776A>G | p.T259C | Missense | E13 | Prelingual | Profound | T1‐T2 | Turkey (Kalay et al., 2005) |
| 776+1G>A | Splice disruption | Splicing | E13 | Prelingual | Profound | – | Iran (Hildebrand et al., 2010) |
| 797T>C | p.I266T | Missense | E13 | Prelingual | Severe to profound | – | China (Wang et al., 2018) |
| 821C>T | p.P274L | Missense | E13 | Prelingual | Profound | T2 | Turkey (Kalay et al., 2005) |
| 830A>G | p.Y277C | Missense | E13 | Prelingual | Severe to profound | T2 | Pakistan (Santos et al., 2005) |
| 884+1G>A | Splice disruption | Splicing | E13 | Prelingual | Severe to profound | – | Pakistan (Kurima et al., 2002) |
| 1083_1087del | p.R362PfsX6 | Frameshift | E15 | Prelingual | Profound | T2‐T3 | Turkey (Kalay et al., 2005) |
| 1114G>A | p.V372M | Missense | E15 | Prelingual | Severe to profound | T3 | Pakistan (Santos et al., 2005) |
| 1165C>T | p.R389X | Nonsense | E15 | Congenital | Profound | T3‐T4 | Tunisia (Tlili et al., 2008), Jordan (Hilgert et al., 2008) |
| 1166G>A | p.R389Q | Missense | E15 | Congenital | Severe to profound | T3‐T4 | Turkey (Hilgert et al., 2008) |
| 1209G>C | p.W403C | Missense | E15 | Prelingual | Severe to profound | T3‐T4 | (Yang et al., 2013) |
| 1253T>A | p.M418K | Missense | E16 | Prelingual | Severe to profound | T4 | China (Wang et al., 2018) |
| 1283C>A | p.Ala428Asp | Missense | E16 | Prelingual | Severe to profound | T4 | India (Singh et al., 2017) |
| 1330G>A | p.G444R | Missense | E16 | Congenital/Prelingual | Profound | T4 | Turkey (Sirmaci et al., 2009) |
| 1333C>T | p.R445C | Missense | E16 | Congenital/Prelingual | Severe to profound | T4 | Turkey (Sirmaci et al., 2009) |
| 1334G>A | p.R445H | Missense | E16 | Prelingual | Profound | T4 | Turkey (Kalay et al., 2005) |
| c.1404+1G > T | Splice disruption | Splicing | E16 | Prelingual | Moderate to severe | ‐ | Pakestan (Imtiaz et al., 2016) |
| 1534C>T | p.R512X | Nonsense | E17 | Prelingual | Severe to profound | T4‐T5 | Pakistan (Kurima et al., 2002) |
| 1541C>T | p.P514L | Missense | E17 | Prelingual | Severe to profound | T4‐T5 | Pakistan (Kitajiri et al., 2007) |
| 1543T>C | p.C515R | Missense | E17 | Prelingual | Severe to profound | T4‐T5 | Pakistan (Kitajiri et al., 2007) |
| c.1566+1G>A | Splice disruption | Splicing | – | Prelingual | Severe to profound | – | India (Ganapathy et al., 2014) |
| 1586_1587del | ‐ | Frameshift | E18 | – | Severe to profound | – | Iran (Sadeghian et al., 2019) |
| 1589_1590del | p.S530X | Nonsense | E18 | – | Profound | – | Iran (Bademci et al., 2016) |
| 1703A>G | p.Y568C | Missense | E19 | – | Profound | – | Iran (Sloan‐Heggen et al., 2015) |
| 1714G>A | p.D572N | Missense | E19 | Prelingual | Severe to profound | – | Chine (Wang et al., 2018) |
| 1763+3A>G | p.W588WfsX81 | Frameshift | I19 | Post‐lingual | Profound | – | Netherlands (de Heer et al., 2011) |
| 1764G>A | p.W588X | Nonsense | E20 | Congenital | Profound | T4‐T5 | Tunisia (Tlili et al., 2008) |
| 1810C>T | p.R604X | Nonsense | E20 | Congenital | Severe to profound | T4‐T5 | Greece (Hilgert et al., 2008) |
| 1810C>G | p.R604G | Missense | E20 | Prelingual | Severe | T4 | Morocco (Bakhchane et al., 2015) |
| 1960A>G | p.M654V | Missense | E20 | Prelingual | Severe to profound | T5 | India (Kurima et al., 2002) |
| 1979C>T | p.P660L | Missense | E20 | Congenital | Profound | T5‐T6 | China (Sadeghian et al., 2019) |
| 2004T>G | p.S668R | Missense | E21 | Prelingual | Severe to profound | T5‐T6 | Pakistan (Kitajiri et al., 2007; Santos et al., 2005) |
| 2030T>C | p.I677T | Missense | E21 | Congenital/Prelingual | Profound | T5‐T6 | Turkey (Sirmaci et al., 2009) |
| 2035G>A | p.E679K | Missense | E21 | Prelingual | Severe to profound | T5‐T6 | Pakistan (Santos et al., 2005) |
| 2260+2T>A | Splice disruption | Splicing | I23 | Prelingual | Severe to profound | – | Tunisia (Riahi et al., 2014) |
| 1696_2283del | Genomic deletion | Deletion | – | Congenital/Prelingual | Profound | – | Turkey (Sirmaci et al., 2009) |