Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Prevention |
RCV003402966 | SCV004119215 | uncertain significance | COL11A2-related disorder | 2022-10-06 | criteria provided, single submitter | clinical testing | The COL11A2 c.3743C>T variant is predicted to result in the amino acid substitution p.Pro1248Leu. On an alternative transcript (NM_080679), this variant is referred to as c.3422C>T (p.Pro1141Leu). This variant was reported in an individual with hearing loss (Supplementary Table S3, Sloan-Heggen et al. 2016. PubMed ID: 26969326). This variant is reported in 0.023% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-33137215-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Labcorp Genetics |
RCV003553929 | SCV004293285 | benign | not provided | 2023-10-04 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV004701057 | SCV005203744 | uncertain significance | not specified | 2024-07-03 | criteria provided, single submitter | clinical testing | Variant summary: COL11A2 c.3743C>T (p.Pro1248Leu) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The frequency data for this variant in gnomAD is considered unreliable, as metrics indicate poor data quality at this position. c.3743C>T has been reported in the literature in a heterozygous individuals affected with COL11A2-Related Disorders (Sloan-Heggen_2016). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 26969326). ClinVar contains an entry for this variant (Variation ID: 2636531). Based on the evidence outlined above, the variant was classified as uncertain significance. |