Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001008132 | SCV001167891 | pathogenic | not provided | 2022-01-31 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 20170898, 31980526, 23340767, 20170899) |
Revvity Omics, |
RCV000000160 | SCV002022410 | pathogenic | Autosomal recessive nonsyndromic hearing loss 79 | 2022-05-30 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001008132 | SCV002246392 | pathogenic | not provided | 2024-01-11 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gly76Alafs*150) in the TPRN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TPRN are known to be pathogenic (PMID: 20170898, 20170899). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with autosomal recessive nonsyndromic deafness (PMID: 20170898, 20170899, 23340767). It has also been observed to segregate with disease in related individuals. This variant is also known as c.42_52del. ClinVar contains an entry for this variant (Variation ID: 137). For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000000160 | SCV002547792 | pathogenic | Autosomal recessive nonsyndromic hearing loss 79 | 2022-04-29 | criteria provided, single submitter | clinical testing | Variant summary: C9orf75 c.225_235del11 (p.Gly76AlafsX150) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 0.00014 in 35206 control chromosomes (gnomAD). c.225_235del11 (also known as c.42_52del11) has been reported in the literature in multiple individuals affected with Autosomal Recessive Nonsyndromic Hearing Loss 79 (e.g. Rehman_2010, Li_2010, Bashir_2013). These data indicate that the variant is very likely to be associated with disease. Three ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Neuberg Supratech Reference Laboratories Pvt Ltd, |
RCV000000160 | SCV004176600 | pathogenic | Autosomal recessive nonsyndromic hearing loss 79 | 2023-03-01 | criteria provided, single submitter | clinical testing | The frameshift c.225_235del(p.Gly76AlafsTer150) variant in TPRN gene has been observed in individual(s) with autosomal recessive nonsyndromic deafness (Bashir et. al., 2013; Rehman et. al., 2010). It has also been observed to segregate with disease in related individuals. This variant is also known as c.42_52del. The p.Gly76AlafsTer150 variant is novel (not in any individuals) in 1000 Genomes. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has been reported to the ClinVar database as Pathogenic by multiple submitters. This variant causes a frameshift starting with codon Glycine 76, changes this amino acid to Alanine residue, and creates a premature Stop codon at position 150 of the new reading frame, denoted p.Gly76AlafsTer150. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TPRN are known to be pathogenic (Rehman et. al., 2010). For these reasons, this variant has been classified as Pathogenic. In the absence of another reportable variant in TPRN gene, the molecular diagnosis is not confirmed. |
OMIM | RCV000000160 | SCV000020303 | pathogenic | Autosomal recessive nonsyndromic hearing loss 79 | 2010-03-12 | no assertion criteria provided | literature only | |
Comprehensive Medical Genetic Center, |
RCV000000160 | SCV002549689 | pathogenic | Autosomal recessive nonsyndromic hearing loss 79 | no assertion criteria provided | clinical testing |